Thiazolyl amide derivatives

ABSTRACT

The present invention relates to novel compounds, to a process for their preparation and to their use as medicaments, in particular as antiviral medicaments.

[0001] The present invention relates to novel compounds, namelythiazolyl amide derivatives, to processes for their preparation and totheir use as medicaments, in particular as antiviral medicaments.

[0002] 2-Aminothiazole-5-sulphonamides are known from the publication C.Ziegler et al., J. Org. Chem. 25, 1960, 1454-1455. Moreover, the GermanOffenlegungsschrift 2101640 describes N-thiazol-2-yl-amides and -ureashaving herbicidal action.

[0003] WO97/24343 relates to phenylthiazole derivatives havinganti-herpes-virus properties.

[0004] WO99/42455 likewise relates to phenylthiazole derivatives havinganti-herpes-virus properties.

[0005] WO99/47507 relates to 1,3,4-thiadiazole derivatives havinganti-herpes-virus properties.

[0006] The present invention relates to novel compounds which arethiazolyl amide derivatives of the general formula (I):

[0007] in which

[0008] R¹ represents hydrogen, halogen, (C₁-C₆)-alkyl, (C₁-C₆)-alkoxy,amino-(C₁-C₆)-alkyl or halogeno-(C₁-C₆)-alkyl,

[0009] R² and R³ are identical or different and represent hydrogen,(C₁-C₆)-alkoxy, (C₃-C₈)-cycloalkyl or biphenylaminocarbonyl, or

[0010]  represent (C₁-C₆)-alkyl which is optionally substituted by 1 to3 substituents selected from the group consisting of (C₃-C₆)-cycloalkyl,(C₁-C₆)-alkoxy, halogen, hydroxyl, amino, tri-(C₁-C₆)-alkylsilyloxy,radicals of the formula

[0011]  in which R^(2′) represents hydrogen or (C₁-C₄)-alkyl,

[0012]  a 5- or 6-membered aromatic heterocycle having up to 3heteroatoms from the group consisting of S, N and O, where anitrogen-containing heterocycle may also be attached via the nitrogenatom, a 3- to 8-membered saturated or unsaturated nonaromaticheterocycle having up to 3 heteroatoms from the group consisting of S, Nand O, which may optionally be attached via a nitrogen atom, and(C₆-C₁₀)-aryl which for its part may be substituted by hydroxyl or(C₁-C₆)-alkoxy, or

[0013]  represent a group of the formula

[0014]  in which R⁸ and R⁹ are identical to or different from oneanother and represent hydrogen and (C₁-C₄)-alkyl, or represent a groupof the formula

[0015]  in which R¹⁰ is the side-group of a naturally occurring α-aminoacid, or

[0016]  represent a group of the formula

[0017]  in which R¹¹ represents (C₁-C₄)-alkyl and R¹² representshydrogen, (C₁-C₄)-alkyl or represents a group of the formula

[0018]  in which R^(10′) is the side-group of a naturally occurringα-amino acid, or

[0019] R² and R³ together with the nitrogen atom form a 5- or 6-memberedsaturated heterocycle which may optionally contain an oxygen atom,

[0020] R⁴ represents hydrogen, (C₁-C₆)-acyl, (C₂-C₆)-alkenyl,(C₃-C₈)-cycloalkyl, or

[0021] R⁴ represents (C₁-C₆)-alkyl which may optionally be substitutedby 1 to 3 substituents selected from the group consisting of halogen,hydroxyl, (C₃-C₈)-cycloalkyl, (C₁-C₆)-acyl, (C₁-C₆)-alkoxy, carboxyl,

[0022]  in which R^(4′) represents hydrogen, —(OCH₂CH₂)_(n)OCH₂CH₃, inwhich n is 0 or 1, phenoxy, (C₆-C₁₀)-aryl and —NR¹³R¹⁴,

[0023]  in which R¹³ and R¹⁴ are identical or different and representhydrogen, (C₁-C₆)-acyl, (C₁-C₆)-alkyl, carbamoyl, mono- ordi-(C₁-C₆)-alkylamino-(C₁-C₆)-alkyl, mono- ordi-(C₁-C₆)-alkylaminocarbonyl, (C₆-C₁₀)-aryl or (C₁-C₆)-alkoxycarbonyl,or

[0024]  R¹³ and R¹⁴ together with the nitrogen atom form a 5- or6-membered saturated heterocycle which may optionally contain a furtherheteroatom from the group consisting of S and O or a radical of theformula —NR 15, and which may be substituted by oxo,

[0025]  in which

[0026] R¹⁵ represents hydrogen or (C₁-C₄)-alkyl, or

[0027] R⁴ represents (C₁-C₆)-alkyl which is substituted by a 5- or6-membered aromatic, optionally benzo-fused heterocycle having up to 3heteroatoms from the group consisting of S, N and O, where anitrogen-containing heterocycle may also be attached via the nitrogenatom, or which is substituted by

[0028]  radicals of the formulae

[0029]  in which

[0030] R¹⁶ represents hydrogen or (C₁-C₆)-alkyl,

[0031] R¹⁷ and R¹⁸ are identical or different and represent hydrogen,(C₁-C₆)-alkyl or (C₆-C₁₀)-aryl, where abovementioned (C₁-C₆)-alkyl and(C₆-C₁₀)-aryl may optionally be substituted by 1 to 3 substituentsselected from the group consisting of hydroxyl, (C₁-C₆)-alkoxy andhalogen,

[0032] R⁵ represents hydrogen, (C₁-C₆)-alkyl, halogen, amino, mono- ordi-(C₁-C₆)-alkylamino or represents (C₁-C₆)-alkanoylamino,

[0033] R⁶ represents phenyl which may optionally be substituted by oneto three substituents selected from the group consisting of

[0034] halogen,

[0035] (C₆-C₁₀)-aryl which may optionally be substituted by 1 to 3substituents selected from the group consisting of (C₁-C₆)-alkanoyl,(C₁-C₆)-alkoxy, (C₁-C₆)-alkyl, halogen, (C₁-C₆)-alkoxycarbonyl, nitro,halogeno-(C₁-C₆)-alkyl, halogeno-(C₁-C₆)-alkoxy, amino,(C₁-C₆)-alkylthio, hydroxyl, carboxyl, carbamoyl, mono- ordi-(C₁-C₆)-alkylaminocarbonyl, mono- or di-(C₁-C₆)-alkanoylamino,(C₁-C₆)-alkoxycarbonylamino, (C₁-C₆)-alkylsulphoxy,(C₁-C₆)-alkylsulphonyl, tri-(C₁-C₆)-alkylsilyloxy, a 3- to 8-memberedsaturated or unsaturated nonaromatic mono- or bicyclic heterocyclehaving up to 3 heteroatoms from the group consisting of S, N and O,which may optionally be attached via a nitrogen atom, and/or cyano,

[0036] (C₁-C₆)-alkoxy,

[0037] (C₁-C₆)-alkoxycarbonyl,

[0038] (C₁-C₆)-alkylthio,

[0039] hydroxyl,

[0040] carboxyl,

[0041] partially fluorinated (C₁-C₆)-alkoxy having up to 6 fluorineatoms,

[0042] (C₁-C₆)-alkyl which is optionally substituted by a radical of theformula

[0043] a 5- or 6-membered aromatic heterocycle having up to 3heteroatoms from the group consisting of S, N and O which may optionallybe attached via a nitrogen atom and which may optionally be substitutedby 1 to 3 substituents selected from the group consisting of(C₁-C₆)-alkanoyl, (C₁-C₆)-alkoxy, (C₁-C₆)-alkyl, halogen,(C₁-C₆)-alkoxycarbonyl, nitro, halogeno-(C₁-C₆)-alkyl,halogeno-(C₁-C₆)-alkoxy, amino, (C₁-C₆)-alkylthio, hydroxyl, carboxyl,carbamoyl, aminocarbonyl, mono- or di-(C₁-C₆)-alkylaminocarbonyl, mono-or di-(C₁-C₆)-alkanoylamino, (C₁-C₆)-alkoxycarbonylamino,(C₁-C₆)-alkylsulphoxy, (C₁-C₆)-alkylsuphonyl, a 3- to 8-memberedsaturated or unsaturated nonaromatic mono- or bicyclic heterocyclehaving up to 3 heteroatoms from the group consisting of S, N and O whichmay optionally be attached via a nitrogen atom, and/or cyano,

[0044] a 3- to 8-membered saturated or unsaturated nonaromatic mono- orbicyclic heterocycle having up to 3 heteroatoms from the groupconsisting of S, N and O, which may optionally be attached via anitrogen atom and which may optionally be substituted by 1 to 3substituents selected from the group consisting of oxo, halogen,hydroxyl, (C₁-C₆)-alkoxycarbonyl, (C₁-C₆)-alkoxycarbonylamino,(C₁-C₆)-alkyl, halogeno-(C₁-C₆)-alkyl and hydroxy-(C₁-C₆)-alkyl,

[0045] (C₂-C₆)-alkenyl

[0046]  and groups of the formulae

[0047] —OR¹⁹,

[0048] —NR²⁰R²¹ or —CO—NR²²R²³,

[0049] carbazole, dibenzofuran or dibenzothiophene,

[0050] xanthene or 9,10-dihydroacridine,

[0051]  in which R¹⁹ is phenyl which for its part is optionallysubstituted by a group of the formula —NR²⁴R²⁵

[0052]  in which

[0053] R²⁴ and R²⁵ are identical or different and represent hydrogen,(C₁-C₆)-alkyl or (C₁-C₆)-acyl, or

[0054] R¹⁹ represents (C₁-C₆)-alkyl which is optionally mono- totrisubstituted by hydroxyl and/or halogen,

[0055] R²⁰ and R²¹ are identical or different and represent hydrogen,carbamoyl, mono- or di-(C₁-C₆)-alkylaminocarbonyl, phenyl, (C₁-C₆)-acylor (C₁-C₆)-alkyl,

[0056]  where abovementioned (C₁-C₆)-alkyl is optionally substituted by(C₁-C₆)-alkoxy, (C₁-C₆)-acyl, by phenyl or by a 5- or 6-memberedaromatic heterocycle having up to 3 heteroatoms from the groupconsisting of S, N and O,

[0057]  where abovementioned phenyl and abovementioned aromaticheterocycle are optionally mono- to trisubstituted by identical ordifferent substituents from the group consisting of halogen andhydroxyl, and

[0058]  R²² and R²³ are identical or different and represent hydrogen or(C₁-C₆)-alkyl,

[0059]  and R⁷ may have the meaning of R⁵ and may be identical to ordifferent from R⁵,

[0060] and their salts.

[0061] Physiologically acceptable salts of the compounds according tothe invention can be, for example, salts of the substances according tothe invention with mineral acids, carboxylic acids or sulphonic acids.Particular preference is given, for example, to salts with hydrochloricacid, hydrobromic acid, sulphuric acid, phosphoric acid,methanesulphonic acid, ethanesulphonic acid, toluenesulphonic acid,benzenesulphonic acid, naphthalenedisulphonic acid, acetic acid,propionic acid, lactic acid, tartaric acid, citric acid, fumaric acid,maleic acid, or benzoic acid.

[0062] Salts which may furthermore be mentioned are salts with customarybases, such as, for example, alkali metal salts (for example sodium orpotassium salts), alkaline earth metal salts (for example calcium ormagnesium salts) or ammonium salts, derived from ammonia or organicamines, such as, for example, diethylamine, triethylamine,ethyldiisopropylamine, procaine, dibenzylamine, N-methylmorpholine,dihydroabietylamine, 1-ephenamine or methylpiperidine.

[0063] Depending on the substitution pattern, the compounds according tothe invention can exist in stereoisomeric forms which either behave asimage and mirror image (enantiomers), or which do not behave as imageand mirror image (diastereomers). The invention relates both to theenantiomers or diastereomers and their respective mixtures. Like thediastereomers, the racemic forms can be separated into thestereoisomerically uniform components in a known manner.

[0064] The scope of the invention includes those compounds which areonly converted into the actual active compounds of the formula (I) onceinside the body (so-called prodrugs).

[0065] (C₁-C₆)-Alkyl advantageously represents a straight-chain orbranched alkyl radical having from 1 to 6 carbon atoms. Preference isgiven to a straight-chain or branched alkyl radical having 1 to 4 carbonatoms (C₁-C₄). Examples which may be mentioned are:

[0066] methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl,tert-butyl, n-pentyl and n-hexyl. Particular preference is given to astraight-chain or branched alkyl radical having 1 to 3 carbon atoms((C₁-C₃)-alkyl).

[0067] Halogeno-(C₁-C₆)-alkyl advantageously represents a (C₁-C₆)-alkylgroup which can be defined as above and which has 1 to 3 halogen atoms,namely F, Cl, Br and/or I, preferably chlorine or fluorine, assubstituents; examples which may be mentioned are trifluoromethyl,fluoromethyl, etc.

[0068] Hydroxy-(C₁-C₆)alkyl advantageously represents a (C₁-C₆)-alkylgroup which can be defined as above and which has 1 to 3 hydroxyl groupsas substituents; examples which may be mentioned are hydroxymethyl etc.

[0069] (C₁-C₆)-Alkenyl in the context of the invention advantageouslyrepresents a straight-chain or branched alkenyl radical having 2 to 6carbon atoms. Examples which may be mentioned are: ethenyl,n-prop-2-en-1-yl and n-but-2-en-1-yl. Preference is given to astraight-chain or branched alkenyl radical having 2 to 4 carbon atoms.

[0070] (C₁-C₆)-Alkoxy advantageously represents a straight-chain orbranched alkoxy radical having 1 to 6 carbon atoms. Preference is givento a straight-chain or branched alkoxy radical having 1 to 4 carbonatoms (C₁-C₄). Examples which may be mentioned are: methoxy, ethoxy,n-propoxy, isopropoxy, tert-butoxy, n-pentoxy and n-hexoxy. Particularpreference is given to a straight-chain or branched alkoxy radicalhaving 1 to 3 carbon atoms-(C₁-C₃).

[0071] Halogeno-(C₁-C₆)-alkoxy advantageously represents mono- orpolyhalogenated (C₁-C₆)-alkoxy. With respect to the (C₁-C₆)-alkoxymoiety and the definition of halogen, reference is made to the abovedefinition. Halogeno-(C₁-C₆)-alkoxy includes, for example, partiallymono- or polychlorinated and/or -fluorinated or -perfluorinated(C₁-C₆)-alkoxy, such as trifluoromethoxy, fluoromethoxy, chloromethoxy,pentafluoroethoxy, trifluoromethylmethoxy, etc.

[0072] Partially fluorinated (C₁-C₆)-alkoxy having up to 6 fluorineatoms advantageously represents a straight-chain or branched alkoxyradical having 1 to 6 carbon atoms which may be substituted by 1 to 6,preferably 1 to 4, more preferably 1 to 3, fluorine atoms. Preference isgiven to a straight-chain or branched alkoxy radical having 1 to 4carbon atoms and 1 to 4 fluorine atoms. Examples which may be mentionedare: methoxy, ethoxy, n-propoxy, isopropoxy, tert-butoxy, n-pentoxy andn-hexoxy, which in each case have 1 to 4 fluorine atoms. Particularpreference is given to (1,3-difluoroprop-2-yl)-oxy and1,1,2,2-tetrafluorethoxy.

[0073] (C₁-C₆)-Alkylthio advantageously represents a straight-chain orbranched alkylthio radical having 1 to 6 carbon atoms. Preference isgiven to a straight-chain or branched alkylthio radical having 1 to 4carbon atoms (C₁-C₄). Examples which may be mentioned are: methylthio,ethylthio, n-propylthio, isopropylthio, tert-butylthio, n-pentylthio andn-hexylthio. Particular preference is given to a straight-chain orbranched alkylthio radical having 1 to 3 carbon atoms (C₁-C₃)-alkylthio.

[0074] (C₁-C₆)-Alkoxycarbonyl advantageously represents a straight-chainor branched alkoxycarbonyl radical having 1 to 6 carbon atoms.Preference is given to a straight-chain or branched alkoxycarbonylradical having 1 to 4 carbon atoms (C₁-C₄). Examples which may bementioned are: methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl,isopropoxycarbonyl and tert-butoxycarbonyl. Particular preference isgiven to a straight-chain or branched alkoxycarbonyl radical having 1 to4 carbon atoms (C₁-C₄).

[0075] Mono- or di-(C₁-C₆)-alkylaminocarbonyl in the context of theinvention advantageously represents a carbamoyl group (H₂N—CO—), inwhich one or both hydrogen atoms are replaced by a (C₁-C₆)-alkyl group.With respect to the definition of the (C₁-C₆)-alkyl group, reference ismade to the above explanation of (C₁-C₆)-alkyl. Examples which may bementioned are methylaminocarbonyl, dimethylamino, etc.

[0076] Mono- or di-(C₁-C₆)-acylamino in the context of the inventionadvantageously represents an amino group (H₂N—) in which one or bothhydrogen atoms are replaced by a (C₁-C₆)-acyl group. With respect to thedefinition of the (C₁-C₆)-acyl group, reference is made to the aboveexplanation of (C₁-C₆)-acyl. An example which may be mentioned is(C₁-C₆)-alkanoyl, as mentioned in the definition of (C₁-C₆)-acyl.

[0077] (C₁-C₆)-Alkylsulphoxy advantageously represents a(C₁-C₆)-alkyl-S(═O)— group, where, with respect to the (C₁-C₆)-alkylgroup, reference can be made to the relevant definition above.

[0078] (C₁-C₆)-Alkylsulphonyl advantageously represents a(C₁-C₆)-alkyl-SO₂ group where, with respect to the (C₁-C₆)-alkyl group,reference can be made to the relevant definition above.

[0079] (C₆-C₁₀) Aryl generally represents an aromatic radical having 6to 10 carbon atoms. Preferred aryl radicals are phenyl and naphthyl.

[0080] (C₁-C₆)-Acyl in the context of the invention advantageouslyrepresents a straight-chain or branched acyl radical having 1 to 6carbon atoms. Examples which may be mentioned are: formyl, acetyl,ethanoyl, propanoyl, isopropanoyl, butanoyl, isobutanoyl and pentanoyl.Preference is given to a straight-chain or branched acyl radical having1 to 4 carbon atoms. Particular preference is given to acetyl andethanoyl.

[0081] (C₃-C₈)-Cycloalkyl in the context of the invention representscyclopropyl, cyclopentyl, cyclobutyl, cyclohexyl, cycloheptyl orcyclooctyl. Cyclopropyl, cyclopentyl and cyclohexyl may be mentioned asbeing preferred. The meaning of (C₃-C₆)-cycloalkyl is correspondinglyadvantageously cyclopropyl, cyclopentyl, cyclobutyl, cyclohexyl.

[0082] Halogen in the context of the invention generally representsfluorine, chlorine, bromine and iodine. Preference is given to fluorine,chlorine and bromine. Particular preference is given to fluorine andchlorine.

[0083] (C₁-C₆)-Alkanoyl in the context of the invention representsformyl and (C₁-C₅)-alkylcarbonyl groups, where (C₁-C₅)-alkyl may be astraight-chain or branched alkyl group having 1 to 5 carbon atoms, forexample acetyl, propionyl, butyryl, pentanoyl.

[0084] A 5- or 6-membered aromatic heterocycle having up to 3heteroatoms from the group consisting of S, O and N represents, forexample, pyridyl, pyrimidyl, thienyl, furyl, pyrrolyl, thiazolyl,N-triazolyl, oxazolyl or imidazolyl. Preference is given to pyridyl,furyl, thiazolyl and N-triazolyl.

[0085] A 5- or 6-membered aromatic benzo-fused heterocycle having up to3 heteroatoms from the group consisting of S, O and N represents, forexample, benzimidazolyl.

[0086] A 5- or 6-membered saturated heterocycle attached via a nitrogenatom, which can be formed from two substituent groups together with thenitrogen atom to which they are attached, and which may optionallycontain a further heteroatom from the group consisting of S and O or aradical of the formula —NR 5, in which R¹⁵ is as defined above,generally represents, in the context of the invention, morpholinyl,piperidinyl, piperazinyl, methylpiperazinyl, thiomorpholinyl orpyrrolidinyl. Particular preference is given to morpholinyl,piperidinyl, pyrrolidinyl and thiomorpholinyl.

[0087] A 3- to 8-membered saturated or unsaturated nonaromaticheterocycle which is optionally attached via a nitrogen atom and whichhas up to 3 heteroatoms from the group consisting of S, N and Oincludes, for example, the abovementioned 5- or 6-membered saturatedheterocycles which are attached via a nitrogen atom, and also 3-, 7- and8-membered heterocycles, such as, for example, aziridines (for example1-azacyclopropan-1-yl), azetidines (for example 1-azacyclobutan-1-yl)and azepines (for example 1-azepan-1-yl). The unsaturatedrepresentatives may contain 1 or 2 double bonds in the ring.

[0088] The side-group of a naturally occurring α-amino acid in themeaning of R¹⁰ includes, for example: hydrogen (glycine), methyl(alanine), propan-2-yl (valine), 2-methyl-propan-1-yl (leucine),1-methyl-propan-1-yl (isoleucine), a propan-1,3-diyl group which isattached to the nitrogen atom of the amino group (proline), a2-hydroxypropane-1,3-diyl group which is attached to the nitrogen atomof the amino group (hydroxyproline), a group of the formula

[0089] (tryptophan), a benzyl group (phenylalanine), a methylthioethylgroup (methionine), hydroxymethyl (serine), p-hydroxybenzyl (tyrosine),1-hydroxy-ethan-1-yl (threonine), mercaptomethyl (cysteine),carbamoylmethyl (asparagine), carbamoylethyl (glutamine), carboxymethyl(aspartic acid), carboxyethyl (glutamic acid), 4-aminobutan-1-yl(lysine), 3-guanidinopropan-1-yl (arginine), imidazol-4-ylmethyl(histidine), 3-ureidopropan-1-yl (citrulline), mercaptoethyl(homocysteine), hydroxyethyl (homoserine), 4-amino-3-hydroxybutan-1-yl(hydroxylysine), 3-amino-propan-1-yl (ornithine), etc.

[0090] In a further embodiment, the invention relates to compounds ofthe general formula (I) according to claim 1:

[0091] in which

[0092] R¹ represents hydrogen, halogen, (C₁-C₆)-alkyl, (C₁-C₆)-alkoxy,amino-(C₁-C₆)-alkyl or halogeno-(C₁-C₆)-alkyl,

[0093] R² and R³ are identical or different and represent hydrogen,(C₁-C₆)-alkoxy, (C₃-C₈)-cycloalkyl or biphenylaminocarbonyl, or

[0094] represent (C₁-C₆)-alkyl which is optionally substituted by 1 to 3substituents selected from the group consisting of (C₃-C₆)-cycloalkyl,(C₁-C₆)-alkoxy, halogen, hydroxyl, amino, radicals of the formula

[0095] a 5- or 6-membered aromatic heterocycle having up to 3heteroatoms from the group consisting of S, N and O, where anitrogen-containing heterocycle may also be attached via the nitrogenatom,

[0096] a 3- to 8-membered saturated or unsaturated nonaromaticheterocycle having up to 3 heteroatoms from the group consisting of S, Nand O, which may optionally be attached via a nitrogen atom, and

[0097] (C₆-C₁₀)-aryl, which for its part may be substituted by hydroxylor (C₁-C₆)-alkoxy, or

[0098] represent a group of the formula

[0099] in which R⁸ and R⁹ are identical to or different from one anotherand represent hydrogen and (C₁-C₄)-alkyl, or

[0100] represent a group of the formula

[0101] in which R¹⁰ is the side-group of a naturally occurring α-aminoacid, or

[0102] represent a group of the formula

[0103] in which R¹¹ represents (C₁-C₄)-alkyl and R¹² representshydrogen, (C₁-C₄)-alkyl or represents a group of the formula

[0104] in which R^(10′) is the side-group of a naturally occurringα-amino acid, or

[0105] R² and R³ together with the nitrogen atom form a 5- or 6-memberedsaturated heterocycle which may optionally contain an oxygen atom,

[0106] R⁴ represents hydrogen, (C₁-C₆)-acyl, (C₂-C₆)-alkenyl,(C₃-C₈)-cycloalkyl, or

[0107] R⁴ represents (C₁-C₆)-alkyl which may optionally be substitutedby 1 to 3 substituents selected from the group consisting of halogen,hydroxyl, (C₁-C₆)-acyl, (C₁-C₆)-alkoxy,

[0108]  —(OCH₂CH₂)_(n)OCH₂CH₃, in which n is 0 or 1, phenoxy,(C₆-C₁₀)-aryl and —NR¹³R¹⁴,

[0109] in which R¹³ and R¹⁴ are identical or different and representhydrogen, (C₁-C₆)-acyl, (C₁-C₆)-alkyl, carbamoyl, mono- ordi-(C₁-C₆)-alkylamino-(C₁-C₆)-alkyl, mono- ordi-(C₁-C₆)-alkylaminocarbonyl, (C₆-C₁₀)-aryl or (C₁-C₆)-alkoxycarbonyl,or

[0110] R¹³ and R¹⁴ together with the nitrogen atom form a 5- or6-membered saturated heterocycle which may optionally contain a furtherheteroatom from the group consisting of S and O or a radical of theformula —NR¹⁵ and which may be substituted by oxo,

[0111] in which R¹⁵ represents hydrogen or (C₁-C₄)-alkyl, or

[0112] R⁴ represents (C₁-C₆)-alkyl which is substituted by a 5- or6-membered aromatic, optionally benzo-fused heterocycle having up to 3heteroatoms from the group consisting of S, N and O, where anitrogen-containing heterocycle may also be attached via the nitrogenatom, or which is substituted by radicals of the formulae

[0113] in which

[0114] R¹⁶ represents hydrogen or (C₁-C₆)-alkyl,

[0115] R¹⁷ and R¹⁸ are identical or different and represent hydrogen,(C₁-C₆)-alkyl or (C₆-C₁₀)-aryl, where abovementioned (C₁-C₆)-alkyl and(C₆-C₁₀)-aryl may optionally be substituted by 1 to 3 substituentsselected from the group consisting of hydroxyl, (C₁-C₆)-alkoxy andhalogen,

[0116] R⁵ represents hydrogen, (C₁-C₆)-alkyl, halogen, amino, mono- ordi-(C₁-C₆)-alkylamino or represents (C₁-C₆)-alkanoylamino,

[0117] R⁶ represents phenyl which may optionally be substituted by oneto three substituents selected from the group consisting of

[0118] halogen,

[0119] (C₆-C₁₀)-aryl which may optionally be substituted by 1 to 3substituents selected from the group consisting of (C₁-C₆)-alkanoyl,(C₁-C₆)-alkoxy, (C₁-C₆)-alkyl, halogen, (C₁-C₆)-alkoxycarbonyl, nitro,halogeno-(C₁-C₆)-alkyl, halogeno-(C₁-C₆)-alkoxy, amino,(C₁-C₆)-alkylthio, hydroxyl, carboxyl, carbamoyl, mono- ordi-(C₁-C₆)-alkylaminocarbonyl, mono- or di-(C₁-C₆)-alkanoylamino,(C₁-C₆)-alkoxycarbonylamino, (C₁-C₆)-alkylsulphoxy,(C₁-C₆)-alkylsulphonyl, tri-(C₁-C₆)-alkylsilyloxy, a 3- to 8-memberedsaturated or unsaturated nonaromatic mono- or bicyclic heterocyclehaving up to 3 heteroatoms from the group consisting of S, N and O,which may optionally be attached via a nitrogen atom, and/or cyano,

[0120] (C₁-C₆)-alkoxy,

[0121] (C₁-C₆)-alkoxycarbonyl,

[0122] (C₁-C₆)-alkylthio,

[0123] hydroxyl,

[0124] carboxyl,

[0125] partially fluorinated (C₁-C₆)-alkoxy having up to 6 fluorineatoms,

[0126] (C₁-C₆)-alkyl which is optionally substituted by a radical of theformula

[0127] a 5- or 6-membered aromatic heterocycle having up to 3heteroatoms from the group consisting of S, N and O which may optionallybe attached via a nitrogen atom and which may optionally be substitutedby 1 to 3 substituents selected from the group consisting of(C₁-C₆)-alkanoyl, (C₁-C₆)-alkoxy, (C₁-C₆)-alkyl, halogen,(C₁-C₆)-alkoxycarbonyl, nitro, halogeno-(C₁-C₆)-alkyl,halogeno-(C₁-C₆)-alkoxy, amino, (C₁-C₆)-alkylthio, hydroxyl, carboxyl,carbamoyl, mono- or di-(C₁-C₆)-alkylaminocarbonyl, mono- ordi-(C₁-C₆)-alkanoylamino, (C₁-C₆)-alkoxycarbonylamino,(C₁-C₆)-alkylsulphoxy, (C₁-C₆)-alkylsuphonyl, a 3- to 8-memberedsaturated or unsaturated nonaromatic mono- or bicyclic heterocyclehaving up to 3 heteroatoms from the group consisting of S, N and O whichmay optionally be attached via a nitrogen atom, and/or cyano,

[0128] a 3- to 8-membered saturated or unsaturated nonaromatic mono- orbicyclic heterocycle having up to 3 heteroatoms from the groupconsisting of S, N and O, which may optionally be attached via anitrogen atom and which may optionally be substituted by 1 to 3substituents selected from the group consisting of oxo, halogen,hydroxyl, (C₁-C₆)-alkoxycarbonyl, (C₁-C₆)-alkoxycarbonylamino,(C₁-C₆)-alkyl, halogeno-(C₁-C₆)-alkyl and hydroxy-(C₁-C₆)-alkyl,

[0129] and groups of the formulae

[0130] —OR¹⁹,

[0131] —NR²⁰R²¹ or —CO—NR²²R²³,

[0132] in which R¹⁹ is phenyl which for its part is optionallysubstituted by a group of the formula —NR²⁴R²⁵

[0133] in which

[0134] R²⁴ and R²⁵ are identical or different and represent hydrogen,(C₁-C₆)-alkyl or (C₁-C₆)-acyl, or

[0135] R¹⁹ represents (C₁-C₆)-alkyl which is optionally mono- totrisubstituted by hydroxyl and/or halogen,

[0136] R²⁰ and R²¹ are identical or different and represent hydrogen,carbamoyl, mono- or di-(C₁-C₆)-alkylaminocarbonyl, phenyl, (C₁-C₆)-acylor (C₁-C₆)-alkyl,

[0137]  where abovementioned (C₁-C₆)-alkyl is optionally substituted by(C₁-C₆)-alkoxy, (C₁-C₆)-acyl, by phenyl or by a 5- or 6-memberedaromatic heterocycle having up to 3 heteroatoms from the groupconsisting of S, N and O,

[0138]  where abovementioned phenyl and abovementioned aromaticheterocycle are optionally mono- to trisubstituted by identical ordifferent substituents from the group consisting of halogen andhydroxyl, and

[0139] R²² and R²³ are identical or different and represent hydrogen or(C₁-C₆)-alkyl,

[0140] and R⁷ may have the meaning of R⁵ and may be identical to ordifferent from R⁵,

[0141] and their salts.

[0142] In a preferred embodiment, the invention relates to compounds ofthe general formula (I) in which R¹ represents hydrogen or(C₁-C₆)-alkyl.

[0143] In a further preferred embodiment, the invention relates tocompounds of the general formula (I) in which R² and R³ eachindependently represent hydrogen or (C₁-C₆)-alkyl.

[0144] In a further preferred embodiment, the invention relates tocompounds of the general formula (I) in which R⁴ represents hydrogen or(C₁-C₆)-alkyl.

[0145] In a further preferred embodiment, the invention relates tocompounds of the general formula (I) in which R⁵ represents hydrogen.

[0146] In a further preferred embodiment, the invention relates tocompounds of the general formula (I) in which

[0147] R⁶ represents phenyl which may optionally be substituted by oneto three substituents selected from the group consisting of

[0148] halogen,

[0149] (C₆-C₁₀)-aryl which may optionally be substituted by 1 to 3substituents selected from the group consisting of (C₁-C₆)-alkanoyl,(C₁-C₆)-alkoxy, (C₁-C₆)-alkyl, halogen, (C₁-C₆)-alkoxycarbonyl, nitro,halogeno-(C₁-C₆)-alkyl, halogeno-(C₁-C₆)-alkoxy, amino, hydroxyl, mono-or di-(C₁-C₆)-alkylamino, mono- or di-(C₁-C₆)-alkanoylamino,(C₁-C₆)-alkoxycarbonylamino, and/or cyano,

[0150] a 5- or 6-membered aromatic heterocycle having up to 3heteroatoms from the group consisting of S, N and O, which mayoptionally be attached via a nitrogen atom and which may optionally besubstituted by 1 or 2 halogen atoms.

[0151] In a further preferred embodiment, the invention relates tocompounds having the following formula:

[0152] in which

[0153] R¹, R², R³, R⁴, R⁵ and R⁷ are each as defined in claim 1,

[0154] R²⁶ and R²⁷ are identical or different and represent hydrogen,halogen, (C₁-C₆)-alkoxy, (C₁-C₆)-alkoxycarbonyl, (C₁-C₆)-alkylthio,hydroxyl, carboxyl, partially fluorinated (C₁-C₆)-alkoxy having up to 6fluorine atoms, (C₁-C₆)-alkyl, a group of the formula —OR¹⁹, —NR²⁰R²¹ or—CO—NR²²R²³, in which

[0155] R¹⁹ represents phenyl which for its part is optionallysubstituted by a group of the formula —NR²⁴R²⁵,

[0156] in which

[0157] R²⁴ and R²⁵ are identical or different and represent hydrogen,(C₁-C₆)-alkyl or (C₁-C₆)-acyl, or

[0158] R¹⁹ represents (C₁-C₆)-alkyl which is optionally mono- totrisubstituted by hydroxyl and/or halogen,

[0159] R²⁰ and R²¹ are identical or different and represent hydrogen,carbamoyl, mono- or di-(C₁-C₆)-alkylaminocarbonyl, phenyl, (C₁-C₆)-acylor (C₁-C₆)-alkyl,

[0160]  where abovementioned (C₁-C₆)-alkyl is optionally substituted by(C₁-C₆)-alkoxy, (C₁-C₆)-acyl, phenyl or by a 5- or 6-membered aromaticheterocycle having up to 3 heteroatoms from the group consisting of S, Nand O,

[0161]  where abovementioned phenyl and abovementioned aromaticheterocycle are optionally mono- to trisubstituted by identical ordifferent substituents from the group consisting of halogen andhydroxyl, and

[0162] R²² and R²³ are identical or different and represent hydrogen or(C₁-C₆)-alkyl,

[0163] R²⁸ represents (C₆-C₁₀)-aryl, which may optionally be substitutedby 1 to 3 substituents selected from the group consisting of(C₁-C₆)-alkanoyl, (C₁-C₆)-alkoxy, (C₁-C₆)-alkyl, halogen,(C₁-C₆)-alkoxycarbonyl, nitro, halogen-(C₁-C₆)-alkyl,halogen-(C₁-C₆)-alkoxy, amino, (C₁-C₆)-alkylthio, hydroxyl, carboxyl,carbamoyl, mono- or di-(C₁-C₆)-alkylaminocarbonyl, mono- ordi-(C₁-C₆)-alkanoylamino, (C₁-C₆)-alkoxycarbonylamino,(C₁-C₆)-alkylsulphoxy, (C₁-C₆)-alkylsulphonyl,tri-(C₁-C₆)-alkylsilyloxy, a 3- to 8-membered saturated or unsaturatednonaromatic mono- or bicyclic heterocycle having up to 3 heteroatomsfrom the group consisting of S, N and O, which may optionally beattached via a nitrogen atom, and/or cyano, or

[0164] R²⁸ represents a 5- or 6-membered aromatic heterocycle having upto 3 heteroatoms from the group consisting of S, N and O, which mayoptionally be attached via a nitrogen atom and which may optionally besubstituted by 1 to 3 substituents selected from the group consisting of(C₁-C₆)-alkanoyl, (C₁-C₆)-alkoxy, (C₁-C₆)-alkyl, halogen,(C₁-C₆)-alkoxycarbonyl, nitro, halogeno-(C₁-C₆)-alkyl,halogeno-(C₁-C₆)-alkoxy, amino, (C₁-C₆)-alkylthio, hydroxyl, carboxyl,carbamoyl, mono- or di-(C₁-C₆)-alkylaminocarbonyl, mono- ordi-(C₁-C₆)-alkanoylamino, (C₁-C₆)-alkoxycarbonylamino,(C₁-C₆)-alkylsulphoxy, (C₁-C₆)-alkylsulphonyl, a 3- to 8-memberedsaturated or unsaturated nonaromatic mono- or bicyclic heterocyclehaving up to 3 heteroatoms from the group consisting of S, N and O,which may optionally be attached via a nitrogen atom, and/or cyano,

[0165] and their salts.

[0166] Particular preference is, for example, given to the compoundN-[5-(aminosulphonyl)-4-methyl-1,3-thiazol-2-yl]-2-[1,1′-biphenyl]4-yl-N-methylacetamideof the formula:

[0167] to the compoundN-[5-(aminosulphonyl)-4-methyl-1,3-thiazol-2-yl]-2-(2′-fluoro[1,1′-biphenyl]-4-yl)-N-methylacetamideof the formula:

[0168] and to the compoundN-[5-(aminosulphonyl)₄-methyl-1,3-thiazol-2-yl]-N-methyl-2-[4-(2-pyridinyl)phenyl]acetamideof the formula:

[0169] and to pharmaceutically acceptable salts thereof.

[0170] The invention furthermore relates to compounds of the generalformula (IV)

[0171] in which

[0172] R¹, R⁴, R⁵, R⁶ and R⁷ each have the meaning given for the formula(I) and D represents a halogen atom.

[0173] The invention furthermore relates to processes for preparing thecompounds of the general formula (I), characterized in that

[0174] [A] compounds of the general formula (II)

[0175]  in which

[0176] R¹, R², R³ and R⁴ are each as defined above,

[0177] are reacted with compounds of the general formula (III)

[0178] in which

[0179] A represents a leaving group, such as, for example, halogen,preferably chlorine, or hydroxyl, and R⁵, R⁶ and R⁷ are each as definedabove, in inert solvents, if appropriate in the presence of a baseand/or an auxiliary, to give compounds of the formula (I),

[0180] [B] compounds of the general formula (IV)

[0181] in which

[0182] R¹, R⁴, R⁵, R⁶ and R⁷ are each as defined above and D representsa halogen atom, preferably chlorine, are reacted with amines of thegeneral formula (V)

HNR²R³  (V),

[0183] in which

[0184] R² and R³ are each as defined above, in inert solvents, to givecompounds of the formula (I),

[0185] [C] compounds of the general formula (X)

[0186] in which

[0187] R¹, R², R³, R⁴, R⁵, R⁷, R²⁶ and R²⁷ are each as defined above andE represents trifluoromethanesulphonate or halogen, preferably bromineor iodine, are reacted with boronic acids or stannanes of the generalformula (XI)

R²⁸M  (XI),

[0188] in which

[0189] R²⁸ is as defined above and M may be, for example, atri-(C₁-C₆)-alkylstannyl group, such as a trimethylstannyl group, or aboronic acid group, in inert solvents in the presence of palladiumcatalysts, for example tetrakis(triphenylphosphane) palladium(0), ifappropriate in the presence of a base, for example potassium phosphate,at temperatures of 50-140° C., to give compounds of the formula (XIV)

[0190]  and

[0191] [D] compounds of the general formula (XII)

[0192] in which

[0193] R¹, R², R³, R⁴, R⁵, R⁷, R²⁶ and R²⁷ are each as defined above andM is as defined above, are reacted with trifluoromethanesulphonates orhalides of the general formula (XIII):

R²⁸E  (XIII),

[0194] in which

[0195] R²⁸ is as defined above and E is as defined above, in inertsolvents in the presence of palladium catalysts, for exampletetrakis(triphenylphosphane)palladium (0), if appropriate in thepresence of a base, for example potassium phosphate, at temperatures of50-140° C., to give compounds of the formula (XIV).

[0196] The process [A] according to the invention can be illustrated inan exemplary manner by the following equation:

[0197] The abbreviations denote:

[0198] HOBt: 1-hydroxy-1H-benzotriazole

[0199] EDC: N′-(3-dimethylaminopropyl)-N-ethylcarbodiimide×HCl

[0200] DMF: N,N-dimethylformamide

[0201] The process [C] according to the invention can be illustrated inan exemplary manner by the following equation:

[0202] The abbreviation denotes:

[0203] DMF: N,N-dimethylformamide

[0204] The process [D] according to the invention can be illustrated inan exemplary manner by the following equation:

[0205] The abbreviation denotes:

[0206] DMF: N,N-dimethylformamide

[0207] Suitable solvents for the processes [A], [B], [C] and [D] are thecustomary organic solvents which do not change under the reactionconditions. These preferably include ethers, such as diethyl ether,dioxane, tetrahydrofuran, glycol dimethyl ether, or hydrocarbons, suchas benzene, toluene, xylene, hexane, cyclohexane or mineral oilfractions, or halogenated hydrocarbons, such as dichloromethane,trichloromethane, carbon tetrachloride, dichloroethylene,trichloroethylene or chlorobenzene, or ethyl acetate, dimethylsulphoxide, dimethylformamide (DMF) or acetonitrile. It is also possibleto use mixtures of the solvents mentioned. Preference is given to DMF.

[0208] Suitable bases for use in the process [A] according to theinvention are, in general, inorganic or organic bases. These preferablyinclude organic amines (trialkyl(C₁-C₆)amines), such as triethylamine,or heterocycles, such as 1,4-diazabicyclo[2.2.2]octane (DABCO),1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), pyridine, diaminopyridine,N-methylmorpholine or N-methylpiperidine or morpholine. Preference isgiven to triethylamine.

[0209] Suitable auxiliaries are dehydrating or coupling reagents whichare known per se, such as, for example, carbodiimides, such asdiisopropylcarbodiimide, dicyclohexylcarbodiimide (DCC) orN-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDC), or carbonylcompounds, such as carbonyldiimidazole (CDI) or isobutyl chloroformate,or 1,2-oxazolium compounds, such as2-ethyl-5-phenyl-1,2-oxazolium-3′-sulphonate, or phosphorus compounds,such as propanephosphonic anhydride, diphenylphosphoryl azide,benzotriazolyl-N-oxy-tris(dimethylamino)phosphonium hexafluorophosphate(BOP), or uronium compounds, such asO-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate(HBTU), or methanesulphonyl chloride, if appropriate in the presence ofauxiliaries, such as N-hydroxysuccinimide or N-hydroxybenzotriazole.

[0210] In general, the base is employed in an amount of from 0.05 mol to10 mol, preferably from 1 mol to 2 mol, based on 1 mol of the compoundof the formula (III).

[0211] The processes according to the invention are generally carriedout in a temperature range of from −50° C. to +100° C., preferably from−30° C. to +60° C.

[0212] The processes according to the invention are generally carriedout at atmospheric pressure. However, it is also possible to carry outthe processes at elevated pressure or at reduced pressure (for examplein a range of from 0.5 to 5 bar).

[0213] The compounds of the general formula (II) can be prepared, forexample, by converting compounds of the general formula (VI)

[0214] in which

[0215] R¹ is as defined above

[0216] by reaction with the system chlorosulphonic acid/SOCl₂ into thecompounds of the general formula (VII)

[0217] in which

[0218] R¹ is as defined above,

[0219] then, using amines of the general formula (V)

HNR²R³  (V)

[0220] in which

[0221] R² and R³ are each as defined above

[0222] in inert solvents, preparing the compounds of the general formula(VIII)

[0223] in which

[0224] R¹, R² and R³ are each as defined above

[0225] and, in a last step, carrying out a reaction with amines of thegeneral formula (IX)

H₂N—R^(4′)  (IX)

[0226] in which

[0227] R^(4′) has the meaning of R⁴ given above and is identical to ordifferent from R⁴, but is not hydrogen,

[0228] in inert solvents and in the presence of a base.

[0229] The reaction with chlorosulphonic acid/SO₂Cl is initially carriedout at room temperature and then at the reflux temperature of the etherin question.

[0230] The reaction is generally carried out under atmospheric pressure.However, it is also possible to carry out the process at elevatedpressure or at reduced pressure (for example in a range of from 0.5 to 5bar).

[0231] Suitable solvents for the reaction with the amines of the generalformula (V) are alcohols, such as, for example, methanol, ethanol,propanol and isopropanol. Preference is given to methanol.

[0232] The reaction with the amines of the general formula (V) isinitially carried out at room temperature and then at the refluxtemperature of the ether in question.

[0233] The reaction is generally carried out at atmospheric pressure.However, it is also possible to carry out the process at elevatedpressure or at reduced pressure (for example in a range of from 0.5 to 5bar).

[0234] The reaction with the compounds of the general formula (IX) iscarried out in ethers, such as, for example, Methyl ether, dioxane,tetrahydrofuran or glycol dimethyl ether. Preference is given tomethanol.

[0235] Suitable for use as bases are, in general, inorganic or organicbases. These preferably include organic amines (tri(C₁-C₆)alkylamines,such as triethylamine), or heterocycles, such as1,4-diazabicyclo[2.2.2]octane (DABCO),1,8-diazabicyclo-[5.4.0]undec-7-ene (DBU), pyridine, diaminopyridine,methylpiperidine or morpholine. Preference is given to triethylamine.

[0236] In general, the base is employed in an amount of from 0.05 to 10mol, preferably from 1 mol to 2 mol, based on 1 mol of the compound ofthe formula (VIII).

[0237] Some of the compounds of the general formula (VI) are known, orthey can be prepared by customary methods [cf. Hantzsch, Chem. Ber.1927, 60, 2544].

[0238] The compounds of the general formulae (VII) and (VIII) are noveland can be prepared as described above.

[0239] Amines of the general formulae (V) and (IX) are known.

[0240] Compounds of the general formula (III) are known or can beprepared by processes known from the literature.

[0241] Biphenylmethylcarboxylic acid or biphenylacetic acid derivativesof the formula (III) can be prepared in a manner known per se bytransition-metal-catalysed, for example palladium-catalysed, couplingreactions, such as, for example, the Suzuki or Stille coupling. Thepyridylphenylmethylcarboxylic acid derivatives of the formula (III) areknown from the literature (see, for example, M. Artico et al. in Eur. J.Med. Chem. (1992) 27, 219-228), or they can be prepared by processesknown per se. The reaction schemes A, B, C and D below illustrate, in anexemplary manner, the synthesis of biphenylacetic acid derivatives fromthe corresponding boronic acids and the synthesis of pyridylphenylaceticacid derivatives from the corresponding stannyl compounds:

[0242] Compounds of the formula (III) in which R⁵ and R⁷ are fluorine,for example, can be prepared by the process shown in the reaction schemebelow:

[0243] The fluorination with DAST (N,N-diethylaminosulphur trifluoride)is carried out in accordance with J. Fluor. Chem. 61, 1993, 117.

[0244] The invention furthermore relates to the use of the compounds ofthe formula (I) as medicaments.

[0245] The invention furthermore relates to a pharmaceutical compositionwhich comprises a compound of the general formula (I) in a mixture withat least one pharmaceutically acceptable carrier or excipient.

[0246] The invention furthermore relates to the use of a compound of thegeneral formula (I) for preparing a medicament, in particular amedicament for the treatment and/or prevention of viral infections, suchas herpes viruses, in particular Herpes simplex viruses.

[0247] The invention furthermore relates to the use ofN-[5-(aminosulphonyl)-1,3-thiazol-2-yl]acetamide derivatives, preferablyN-[5-(aminosulphonyl)-1,3-thiazol-2-yl]-2-phenylacetamide derivatives,more preferablyN-[5-(aminosulphonyl)-1,3-thiazol-2-yl]-2-[1,1′-biphenyl]-4-ylacetamidederivatives, for preparing medicaments, in particular to the use of thederivatives mentioned for preparing compositions for the treatmentand/or prevention of viral infections in humans or animals, such asinfections caused by herpes viruses, in particular by Herpes simplexviruses. Here, N-[5-(aminosulphonyl)-1,3-thiazol-2-yl]acetamidederivatives, N-[5-(aminosulphonyl)-1,3-thiazol-2-yl]-2-phenylacetamidederivatives andN-[5-(aminosulphonyl)-1,3-thiazol-2-yl]-2-[1,1′-biphenyl]4-ylacetamidederivatives are to be understood as meaning those compounds which arederived from N-[5-(aminosulphonyl)-1,3-thiazol-2-yl]acetamide,N-[5-(aminosulphonyl)-1,3-thiazol-2-yl]-2-phenylacetamide andN-[5-(aminosulphonyl)- 1,3-thiazol-2-yl]-2-[1,1′-biphenyl]4-ylacetamideby the substitution of one or more hydrogen atoms.

[0248] The compounds of the general formula (I) according to theinvention exhibit an unforeseeable surprising spectrum of action. Theyexhibit an antiviral action against representatives of the Herpesviridae group, particularly against Herpes simplex viruses (HSV). Theyare thus suitable for the treatment and prophylaxis of disorders whichare caused by herpes viruses, in particular disorders which are causedby Herpes simplex viruses.

[0249] In Vitro Activity

[0250] Viruses and Cells:

[0251] HSV (HSV-1 Walki, HSV-1F or HSV-2G) was cultivated on Vero cells(ATCC CCL-81) under the following conditions: The cells were grown inM199 medium (5% foetal calf serum, 2 mM glutamine, 100 IU/ml penicillin,100 μg/ml streptomycin) in cell culture bottles at 37° C. and 5% CO₂.The cells were splitted twice per week, in each case 1:4. For theinfection, the medium was removed, the cells were washed with Hank'ssolution, detached using 0.05% trypsin, 0.02% EDTA (Seromed L2143) andincubated at a density of 4×10⁵ cells per ml under the abovementionedconditions for 24 hours. The medium was then removed and the virussolution was added at an m.o.i of <0.05 in a volume of 2 ml per 175 cm²of surface. The medium was incubated under the conditions mentioned forone hour and then made up to a volume of 50 ml per 175 cm² bottle. 3days after the infection, the cultures showed clear signs of acytopathic effect. The virus was released by freezing (−80° C.) andthawing (37° C.) the cultures twice. Cell debris was removed bycentrifugation (300 g, 10 min, 4° C.) and the supernatant was frozendown in aliquots at −80° C.

[0252] The virus titre was determined using a plaque assay. To this end,Vero cells were seeded in 24-well plates at a density of 4×10⁵ cells perwell and, after 24 hours of incubation (37° C., 5% CO₂) infected withdilutions of the virus stock of from 10⁻² to 10⁻¹² (100 μl of inoculum).1 hour after the infection, the medium was removed and the cells werecovered with 1 ml of overlay medium (0.5% methylcellulose, 0.22% sodiumbicarbonate, 2 mM glutamine, 100 IU/ml penicillin, 100 μg/mlstreptomycin, 5% foetal calf serum in MEM-Eagle medium with Earl's salt)and incubated for 3 days. The cells were then fixated using 4% formalinefor 1 hour, washed with water, stained with Giemsa (Merck) for 30 minand then washed and dried. Using a plaque viewer, the virus titre wasdetermined. The virus stocks used for the experiments had a titre of1×10⁶/ml-1×10⁸/ml.

[0253] The anti-HSV action was determined in a screening test system in96-well microtitre plates using various cell lines of neuronal, lymphoidand epithelial origin, such as, for example, Vero (kidney cell line ofthe green monkey), MEF (murine embryonal fibroblasts), HELF (humaneembryonal fibroblasts), NT2 (humane neuronal cell line) or Jurkat(humane lymphoid T-cell line). The effect of the substances on thespreading of the cytopathogenic effect was determined in comparison tothe reference substance acyclovir-sodium (Zovirax^(R)), a clinicallyapproved anti-herpes chemotherapeutic.

[0254] The substances (50 mM), dissolved in DMSO (dimethyl sulphoxide),are examined on microtitre plates (for example 96-well MTP) in finalconcentrations of 250-0.5 μM (micromolar) in two replications (4substances/plate). In the case of potent substances, the dilutions arecontinued for several plates up to 0.5 pM (picomolar). Also examined aretoxic and cytostatic effects of the substances. After an appropriatedilution of the substances (1:2) on the microtitre plate in medium, asuspension of cells (1×10⁴ cells per well) such as, for example, of Verocells in M199 (medium 199) with 5% foetal calf serum, 2 mM glutamine andoptionally 100 IU/ml penicillin and 100 μg/ml streptomycin or of MEFcells in EMEM (Eagle's Minimum Essential Medium) with 10% foetal calfserum, 2 mM glutamine and optionally 100 IU/ml penicillin and 100 μg/mlstreptomycin, or of HELF cells in EMEM with 10% foetal calf serum, 2 mMglutamine and optionally 100 IU/ml penicillin and 100 μg/mlstreptomycin, or of NT2- and Jurkat cells in DMEM (4.5 mg/l glucose pluspyridoxin) with 10% foetal calf serum, 2 mM glutamine, 1 mM sodiumpyruvate, non-essential amino acids and optionally 100 IU/ml penicillinand 100 μg/ml streptomycin is added to each well and the cells in therelevant wells are infected with an appropriate amount of virus (HSV-1 For HSV-2 G having an m.o.i (multiplicity of infection) of 0.0025 forHELF, Vero and MEF cells and an m.o.i of 0.1 for NT2 and Jurkat cells).The plates are then incubated at 37° C. in a CO₂ incubator (5% CO₂) forseveral days. After this time, the cell lawn of, for example, Vero cellsin the substance-free virus controls, starting from 25 infectioncentres, is completely destroyed or lysed by the cytopathogenic effectof the HSV viruses (100% CPE). The plates are initially evaluatedvisually using a microscope and then analysed using a fluorescent dye.To this end, the cell supernatant of all wells of the MTP is aspiratedand the wells are filled with 200 μl of PBS wash solution. The PBS isthen aspirated and all the wells are filled with 200 μl of fluorescentdye solution (fluorescein diacetate, 10 μg/ml in PBS). After anincubation time of 30-90 min, the test plates are read in a fluorescencedetector at an excitation wavelength of 485 nm and an emissionwavelength of 538 nm.

[0255] The results for some compounds are summarized in the table below.TABLE Example IC50 HSV-1 F/Vero IC50 HSV-2 G/Vero 14 0.1 μM 0.75 μM 57<0.01 μM <0.01 μM 8 0.1 μM 0.1 μM 23 0.03 μM 0.1 μM 38 0.05 μM 0.016 μM87 <0.01 μM <0.01 μM 126 0.01 μM 0.1 μM Zovirax 1 μM 3 μM(aciclovir-sodium)

[0256] Here, IC₅₀ is the half-maximal fluorescence intensity withrespect to the non-infected cell control (100% value). The IC₅₀ valuecan also be referenced to a suitable active compound control (seedescription of the assay: infected cells in the presence of suitableconcentrations of a substance having anti-herpes action, such as, forexample, Zovirax 20 μM). This active compound control reachesfluorescence intensities of about 85 to 95% with respect to the cellcontrol.

[0257] Preference is given toN-[5-(aminosulphonyl)-1,3-thiazol-2-yl]acetamide derivatives accordingto the invention whose IC₅₀ (HSV-1 F/Vero) in the in-vitro screeningtest system described above is preferably below 50 μM, more preferablybelow 25 μM and very particularly preferably below 10 μM.

[0258] The compounds according to the invention are thus useful activecompounds for the treatment and prophylaxis of disorders caused byherpes viruses, in particular Herpes simplex viruses. Examples ofindication areas which may be mentioned are:

[0259] 1) Treatment and prophylaxis of herpes infections, in particularHerpes simplex infections in patients displaying symptoms such as Herpeslabialis, Herpes genitalis, and HSV-related keratitis, encephalitis,pneumonia, hepatitis etc.

[0260] 2) Treatment and prophylaxis of herpes infections, in particularHerpes simplex infections, in patients with a suppressed immune system(for example AIDS patients, cancer patients, patients having a geneticimmunodeficiency, transplant patients)

[0261] 3) Treatment and prophylaxis of herpes infections, in particularHerpes simplex infections, in new-born children and infants

[0262] 4) Treatment and prophylaxis of herpes infections, in particularHerpes simplex infections, and in herpes-positive patients, inparticular Herpes-simplex-positive patients, for suppressing recurrence(suppression therapy)

[0263] In-Vivo Action

[0264] Animals:

[0265] 6 week-old female mice, BALB/cABom strain were obtained from acommercial breeder (Bomholtgard Breeding and Research Centre Ltd.).

[0266] Infection:

[0267] The animals were anaesthetized with diethyl ether (Merck) in asealed glass vessel. 50 μl of a dilution of the virus stock (infectiondose 5×10⁴ Pfu) were introduced into the nose of the anaesthetizedanimals using an Eppendorf pipette. In 90-100% of the animals, thisinfection dose causes death by a generalized infection with prominentrespiratory and central-nervous symptoms on average after 5 to 8 days.

[0268] Treatment and Assessment:

[0269] 6 hours after the infection, the animals were treated with dosesof 0.1-100 mg/kg of body mass, 3 times per day, at 7 a.m., 2 p.m. and 7p.m., for a period of 5 days. The substances were pre-dissolved in DMSOand resuspended in tylose/PBS (Hoechst) (final concentration 1.5% DMSO,0.5% tylose in PBS).

[0270] After the last administration, the animals were monitored furtherand the time of death was determined.

[0271] A comparison of the survival curves showed for the compound ofExample 57, for example, an ED₅₀ of about 0.7 mg/kg for HSV-2, whereED₅₀ means that 50% of the animals survive at this dose.

[0272] The novel active compounds can be converted in a known mannerinto the customary formulations, such as tablets, sugar-coated tablets,pills, granules, aerosols, syrups, emulsions, suspensions and solutions,using inert, nontoxic, pharmaceutically suitable carriers and solvents.Here, the therapeutically active compound should in each case be presentin a concentration of about 0.5 to 90% by weight of the total mixture,i.e. in amounts which are sufficient to achieve the dosage rangeindicated.

[0273] The formulations are prepared, for example, by extending theactive compounds with solvents and/or excipients, if appropriate usingemulsifiers and/or dispersants, it being possible, for example, if thediluent used is water, to use, if appropriate, organic solvents asauxiliary solvents.

[0274] Administration is carried out in a customary manner, preferablyorally, parenterally or topically, in particular perlingually orintravenously.

[0275] In the case of parenteral administration, solutions of the activecompounds using suitable liquid carrier materials can be employed.

[0276] In general, it has proved advantageous in the case of intravenousadministration to administer amounts of from approximately 0.001 to 20mg/kg, preferably approximately 0.01 to 10 mg/kg, of bodyweight toachieve effective results, and in the case of oral administration thedose is approximately 0.01 to 30 mg/kg, preferably 0.1 to 20 mg/kg, ofbodyweight.

[0277] In spite of this, it may be necessary, if appropriate, to departfrom the amounts mentioned, namely depending on the bodyweight or on thetype of administration route, on the individual response to themedicament, the manner of its formulation and the time or interval atwhich administration takes place. Thus, in some cases it may be adequateto manage with less than the abovementioned minimum amount, while inother cases the upper limit mentioned must be exceeded. In the case ofthe administration of relatively large amounts, it may be advisable todivide this into several individual administrations over the course ofthe day.

[0278] If appropriate, it may be useful to combine the compoundsaccording to the invention with other active substances, in particularantiviral active substances.

[0279] Starting Materials

EXAMPLE I

[0280] 2-Chloro-4-methyl-1,3-thiazol-5-sulphonyl Chloride

[0281] At room temperature, 150 g (1.12 mol) of2-chloro-4-methyl-1,3-thiazole are added dropwise to a solution of 331 g(2.81 mol) of thionyl chloride in 653 g (5.61 mol) of chlorosulphonicacid. The solution is heated at reflux for 48 h. The mixture is thenpoured into 3 l of ice-water and extracted with 4×400 ml ofdichloromethane. The combined organic phases are washed with 2.5 l ofwater, dried over sodium sulphate and concentrated. Distillation of thecrude product gives 233.7 g of product in the form of an oil. (Bp 87-96°C., 0.7 mbar, GC 98.1%, yield 89.6%).

EXAMPLE II

[0282] 2-Chloro-4-methyl-1,3-thiazol-5-sulphonamide

[0283] At −10° C., 117.7 g (1.8 mol) of a 26% strength aqueous ammoniasolution are added dropwise to a solution of 208 g (95% strength, 0.9mol) of 2-chloro-4-methyl-1,3-thiazole-5-sulphonyl chloride in 1000 mlof tetrahydrofuran. The mixture is stirred without further cooling for 2h and the reaction mixture is then concentrated using a rotaryevaporator. The crude product is used for the next step without furtherpurification.

EXAMPLE III

[0284] 4-Methyl-2-(methylamino)-1,3-thiazole-5-sulphonamide

[0285] At room temperature, 144 g (0.576 mol) of2-chloro-4-methyl-1,3-thiazole-5-sulphonamide are initially charged in600 ml of acetonitrile, and 147 g (1.9 mol) of a 40% strength aqueousmethylamine solution are metered in at room temperature. The reactionmixture is stirred at 50° C. for 6 h and then concentrated using arotary evaporator. The residue is admixed with water, filtered off withsuction and dried.

[0286] Yield: 78 g (66%)

[0287] M.p.: 194° C.

EXAMPLE IV

[0288] 2-Fluorophenylboronic Acid

[0289] Under argon, 155 g (0.86 mol) of 2-fluorobromobenzene areinitially charged in 732 ml of absolute tetrahydrofuran and, at −78° C.,mixed slowly with 600 ml of 1.6 M n-butyllithium in hexane. The mixtureis then stirred at −78° C. for 2 h. At −78° C., 298 ml (1.28 mol) oftrimethyl borate are then added dropwise. After 1 h, cooling is removed,and the reaction mixture is stirred overnight and warmed to roomtemperature. For work-up, the mixture is, at 0° C., mixed with 346 ml ofsaturated ammonium chloride solution, the pH is adjusted to pH 6 using1N HCl and the aqueous phase is extracted 3 times with in each case 250ml of methylene chloride. The combined organic phases are washed withsaturated sodium chloride solution and dried with magnesium sulphate.This gives Example IV in the form of a beige solid.

[0290] Yield: 60.0 g (48%)

[0291] MS (EI, m/z): 140 (80%, [M]⁺), 96 (100%, [C₆H₅F]⁺)

EXAMPLE V

[0292] Methyl (2′-fluoro[1,1′-7biphenyl]-4-yl)acetate

[0293] Under argon, 47.6 g (0.21 mol) of methyl 4-bromophenylacetate areinitially charged in 400 ml of absolute tetrahydrofuran and, at roomtemperature, admixed with 320 ml of 1M sodium carbonate solution and 40g of (0.28 mol) of 2-fluorophenylboronic acid. 7.0 g (0.01 mol) ofbis(triphenylphosphane)palladium(II) chloride are added, and the mixtureis then heated under reflux for 18 h. After cooling, the mixture isdiluted with 500 ml of water and extracted three times with in each case300 ml of ethyl acetate. The combined organic phases are washed with ineach case 400 ml of saturated ammonium chloride solution, water andsaturated sodium chloride solution, dried over magnesium sulphate andfreed from the solvent under reduced pressure. Example V is obtainedafter silica gel filtration (petroleum ether/ethyl acetate 10:1) as acolourless oil.

[0294] Yield: 46.0 g (94%)

[0295]¹H-NMR (500 MHz, CDCl₃, δ/ppm): 3.71 (s, 2H), 3.76 (s, 3H),7.18-7.46 (m, 4H), 7.40 (d, J=8.3 Hz; 2H), 7.56 (dd, J₁=8.3 Hz, J₂=1.7Hz; 2H).

EXAMPLE VI

[0296] (2′-Fluoro[1,1′-biphenyl]4-yl)acetic Acid

[0297] 26.5 g (0.11 mol) of methyl(2′-fluoro[1,1′-biphenyl]-4-yl)acetate are initially charged in 50 ml ofethanol and, at room temperature, admixed with a solution of 12.8 g(0.19 mol) of potassium hydroxide pellets in 25 ml of water. The mixtureis then heated under reflux for 4 h. After cooling, the crude mixture isconcentrated under reduced pressure, and the residue is dissolved in 100ml of water and acidified using conc. hydrochloric acid. The precipitateis filtered off and washed repeatedly with water, and the solid isdried. This gives Example VI in the form of white crystals.

[0298] Yield: 22.7 g (91%)

[0299] M.p.: 102° C.

[0300]¹H-NMR (500 MHz, CDCl₃, δ/ppm): 3.74 (s, 2H), 7.18-7.47 (m, 4H),7.41 (d, J=8.2 Hz; 2H), 7.57 (dd, J₁=8.2 Hz, J₂=1.6 Hz; 2H).

EXAMPLE VII

[0301] Methyl [4-(2-pyridinyl)phenyl]acetate

[0302] Under argon, 7.85 g (34.3 mmol) of methyl 4-bromophenylacetateare initially charged in 95 ml of toluene and, at room temperature,admixed with 7.97 g (61.7 mmol) of diisopropylethylamine, 9.50 g (37.7mmol) of 2-trimethyl-stannylpyridine and 0.4 g (0.3 mmol) oftetrakis(triphenylphosphane)palladium(0). The mixture is then heatedunder reflux for 18 h. After cooling, the mixture is washed with in eachcase 100 ml of 1N hydrochloric acid and saturated sodium bicarbonatesolution. The organic phase is discarded. The acidic and the basicaqueous phase are neutralized and in each case extracted with 100 ml ofdichloromethane, and the combined organic phases are dried over sodiumsulphate and freed from the solvent under reduced pressure. Example VIIis obtained after silica gel chromatography (toluene/ethyl acetategradient 5:1-1:1) as a colourless oil.

[0303] Yield: 1.6 g (19%)

[0304]¹H-NMR (400 MHz, d⁶-DMSO, δ/ppm): 3.64 (s, 3H), 3.76 (s, 2H),7.33-7.40 (m, 1H), 7.39 (d, J=8.2 Hz; 2H), 7.86-7.90 (m, 1H), 7.96 (d,J=8.0 Hz; 1H), 8.05 (d, J=8.2 Hz; 2H), 8.67 (d, J=4.2 Hz, broad; 1H).

EXAMPLE VIII

[0305] [4-(2-Pyridinyl)phenyl]acetic Acid

[0306] 700 mg (3.11 mol) of methyl [4-(2-pyridinyl)phenyl]acetate areinitially charged in 5 ml of tetrahydrofuran and, at room temperature,admixed with 6.2 ml of a 1M potassium hydroxide solution in water. Themixture is then stirred at room temperature for 18 h, most of thesolvent is removed under reduced pressure and the residue is taken up in10 ml of water and adjusted to a pH of about 5 using 2N hydrochloricacid. The aqueous phase was extracted twice, in each case with 10 ml ofdichloromethane, the combined organic phases were dried over magnesiumsulphate and the solvent was removed under reduced pressure, giving thecompound of Example VIII in the form of a solid.

[0307] Yield: 300 mg (46%)

[0308]¹H-NMR (400 MHz, d⁶-DMSO, δ/ppm): 3.76 (s, 2H), 7.45-7.51 (m, 1H),7.50 (d, J=8.3 Hz; 2H), 8.00 (td, J₁=7.7 Hz, J₂=1.9 Hz; 1H), 8.07 (d,J=7.9 Hz; 1H), 8.15 (d, J=8.3 Hz; 2H), 8.78 (dt, J₁=4.0 Hz, J₂=0.9 Hz;1H).

PREPARATION EXAMPLES EXAMPLE 15

[0309]N-[5-(Aminosulphonyl)-4-methyl-1,3-thiazol-2-yl]-2-[1,1′-biphenyl]-4-yl-N-methylacetamide

[0310] 138.2 mg (0.65 mmol) of 4-biphenylacetic acid and 99.7 mg (0.65mmol) of 1-hydroxy-1H-benzotriazole hydrate are initially charged atroom temperature in 5 ml of dimethylformamide. 150 mg (0.72 mmol) of2-methylamino-4-methyl-1,3-thiazole-5-sulphonamide and 138.7 mg (0.72mmol) of N′-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochlorideare added, and the mixture is stirred at room temperature for 72 h. Thereaction mixture is then filtered off with suction and the residue isrecrystallized from 2-propanol. This gives a white solid.

[0311] Yield: 240 mg (83.0%)

[0312] M.p.: 191° C.

[0313]¹H-NMR (300 MHz, d⁶-DMSO, δ/ppm): 2.47 (s, 3H; partially under theDMSO signal), 3.71 (s, 3H), 4.20 (s, 2H), 7.32-7.70 (m, 11H).

EXAMPLE 38

[0314]N-[5-(Aminosulphonyl)-4-methyl-1,3-thiazol-2-yl]-N-methyl-2-[4-(2-pyridinyl)phenyl]acetamide

[0315] At room temperature, 300 mg (1.41 mmol) of[4-(2-pyridinyl)phenyl]acetic acid and 190 mg (1.41 mmol) of1-hydroxy-1H-benzotriazole hydrate are initially charged in 4 ml ofdimethylformamide. 307 mg (1.48 mmol) of2-methylaminomethyl-1,3-thiazole-5-sulphonamide and 284 mg (1.48 mmol)of N′-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride areadded, and the mixture is stirred at room temperature for 18 h. Thesolvent is then removed under reduced pressure, the residue is taken upin toluene and the solvent is once more removed under reduced pressure.The residue is stirred with 15 ml of water and 3 ml of methanol and thenfiltered off, and the filtrate is re-extracted with 20 ml ofdichloromethane. Solid and dichloromethane phase are combined and thesolvent is removed under reduced pressure. This gives the compound ofExample 38 in the form of a white solid.

[0316] Yield: 440 mg (74.0%)

[0317] M.p.: 188-192° C.

[0318] MS (ESI, m/z): 403 (100%, [M+H]⁺)

[0319]¹H-NMR (400 MHz, d⁶-DMSO, δ/ppm): 2.38 (s, 3H; under the DMSOsignal), 3.64 (s, 3H), 4.15 (s, 2H), 7.28-726 (m, 1H), 7.32 (d, J=8 Hz;2H), 7.58 (s, 2H), 7.82-7.96 (m, 2H), 7.98 (d, J=8.0 Hz; 2H), 8.61 (m;1H).

EXAMPLE 57

[0320]N-[5-(Aminosulphonyl)-4-methyl-1,3-thiazol-2-yl]-2-(2′-fluoro[1,1′-biphenyl]-4-yl)-N-methylacetamide

[0321] At room temperature, 17.33 g (73.3 mmol) of(2′-fluoro[1,1′-biphenyl]4-yl)acetic acid and 9.9 g (73.3 mmol) of1-hydroxy-1H-benzotriazole hydrate are initially charged in 600 ml ofdimethylformamide. 16.84 g (81.4 mmol) of2-methylamino-4-methyl-1,3-thiazole-5-sulphonamide and 15.58 g (81.4mmol) of N′-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochlorideare added, and the mixture is stirred at room temperature for 18 h. Mostof the dimethylformamide is removed at 50° C. under high vacuum, and theresidue is taken up in 400 ml of dichloromethane and then washed with ineach case 350 ml of water and 10% citric acid solution. Drying overmagnesium sulphate and removal of the solvent under reduced pressuregives the compound of Example 57 in the form of a white solid.

[0322] Yield: 23.2 g (76.0%)

[0323] M.p.: 211° C.

[0324]¹H-NMR (400 MHz, CDCl₃, δ/ppm): 2.58 (s, 3H), 3.73 (s, 3H), 4.07(s, 2H), 5.91 (s, 2H), 7.13-7.46 (m, 4H), 7.34 (d, J=8.1 Hz; 2H), 7.56(d, broad, J=8.1 Hz; 2H).

EXAMPLE 87

[0325]N-[5-(aminosulphonyl)-4-methyl-1,3-thiazol-2-yl]-2-(2′,5′-difluoro-1,1′-biphenyl-4-yl)-N-methylacetamide

[0326] At room temperature, 1.00 g (4.0 mmol) of(2′,5′-difluoro[1,1′-biphenyl]4-yl)acetic acid and 0.54 g (4.0 mmol) of1-hydroxy-1H-benzotriazole hydrate are initially charged in 15 ml ofdimethylformamide. 0.84 g (4.0 mmol) of2-methylamino-4-methyl-1,3-thiazole-5-sulphonamide and 0.77 g (4.0 mmol)of N′-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride areadded, and the mixture is stirred at room temperature for 18 h. Most ofthe dimethylformamide is removed at 50° C. under high vacuum, and theresidue is stirred 3 times with in each case 50 ml of water and filteredoff, stirred with 50 ml of isopropanol and filtered off once more.Removal of the solvent under reduced pressure gives the compound ofExample 87 in the form of a slightly yellow solid.

[0327] Yield: 0.83 g (47.3%)

[0328] M.p.: 184° C.

[0329]¹H-NMR (400 MHz, DMSO, δ/ppm): 2.49 (s, 3H), 3.71 (s, 3H), 4.24(s, 2H), 7.22-7.46 (m, 3H), 7.38 (d, J=8.2 Hz; 2H), 7.56 (d, J=8.2 Hz;2H), 7.65 (s, 2H).

EXAMPLE 126

[0330]N-[5-(Aminosulphonyl)-4-methyl-1,3-thiazol-2-yl]-N-methyl-2-[4-(1H-pyrazol-1-yl)phenyl]acetamide

[0331] 0.100 g (0.48 mmol) of2-methylamino-4-methyl-1,3-thiazole-5-sulphonamide is dissolved in 10 mlof N,N-dimethylformamide and, at room temperature, admixed with 0.110 g(0.53 mmol) of [4-(1H-pyrazol-1-yl)phenyl]acetic acid, 0.070 g (0.53mmol) of 1-hydroxy-1H-benzotriazole and 0.070 g (0.53 mmol) ofN,N′-diisopropylcarbodiimide. The solution is stirred at roomtemperature overnight. The mixture is then poured into water and theaqueous phase is extracted 3 times with ethyl acetate. The combinedorganic phases are dried with sodium sulphate and concentrated. Thecrude product is subjected to fine purification on a preparative HPLC(RP18 column; mobile phase: acetonitrile/water gradient).

[0332] Yield: 0.11 g (59%)

[0333] LC-MS (Method: SMKL-N1-1Low Vol HCl): retention time: 3.65

[0334] MS(ESI): 783 (2Mz+H), 392 (Mz+H).

[0335]¹H-NMR (300 MHz, DMSO, δ/ppm): 2.48 (s, 3H), 3.72 (s, 3H), 4.20(s, 2H), 6.55 (t, J=2 Hz; 1H), 7.38 (d, J=7 Hz; 2H), 7.65 (s, 2H), 7.75(d, J=2 Hz; 1H), 7.82 (d, J=7 Hz; 2H), 8.49 (d, J=2 Hz; 1H).

[0336] The compounds listed in the table below are prepared analogouslyto the procedures given above: Ex. M.p. Rf Rt [min] No. Structure [° C.]value method 1

186 2

187 3

170 4

180 5

154 6

167 7

192 8

186 9

109 10

128 11

184 12

157 13

153 14

154 15

191 16

133 17

179 18

202 19

163 20

154 21

161 22

158 23

156 24

129 25

105-106 26

142-143 27

139-140 28

oil 5.66 29

179 30

190 31

192 32

193 33

201 34

74-75 35

125-127 36

156 37

oil 0.11 CH2Cl2/ MeOH) 96:4) 38

188-192 39

208 40

177 41

200 42

270 43

125-127 44

168 45

170-172 46

 94 47

188 48

152 49

216 50

108 51

161 52

 80 53

0.30 (CH2Cl2/ MeOH 100:5) 54

160 55

130 56

113 57

211 58

230 59

202 60

145 61

190 62

219 63

68-70 64

152 65

165 66

122 67

168 68

205 69

189 70

130 71

202 72

109 73

204 74

183 75

231 76

234 77

230 78

232 79

264 80

150 81

175 82

0.13 (CH2Cl2/ MeOH/ NH3 10:1:0.1) 83

0.10 (CH2Cl2/ MePH/ NH3 10:1:0.1) 84

202 85

3.38 86

3.1 87

184 88

215 89

138 90

180 91

193 92

136 93

161 94

117 95

154 96

174 97

159 98

203 99

202 100

209 101

167 102

 81 103

221 104

234 105

218 106

225 107

0.38 (CH2Cl2/ MeOH 100:3) 108

225 109

206 110

234 112

128 113

217 114

187 115

156 116

199 117

237 118

204 119

148 120

 79 121

223 122

0.50 (CH2Cl2/ MeOH 100:5) 123

0.57 (CH2Cl2/ MeOH 100:5) 124

4.05 125

159 126

3.65 127

3.45 128

3.1 129

0.14 (CH2Cl2/ MeOH 100:5) 130

130 131

130 132

175

[0337] In the table above, the Rf value denotes the retention index forsilica gel thin-layer chromatography. SMKL-N1-1 denotes the LC-MS methodbelow. Method: SMKL-N1 MS unit type: Finnigan MAT 900S Ionization: ESIpositive HPLC unit type: TSP: P4000, AS3000, UV3000HR Pump head: normalColumn: Symmetry C 18 150 mm × 2.1 mm 5 μm Source: Waters UV detectorDAD: 210 nm Oven temp.: 40° C. Gradient: Time A:% B:% C:% D:% Flow 010.0 45 45 — 0.6 4 90 5 5 — 0.6 9 90 5 5 — 0.6 9.5 10.0 45 45 — 0.8 11.510.0 45 45 — 0.8 12 10.0 45 45 — 0.6 A: CH₃CN B: HCl 0.01 n C: H₂O D: —

1. Compounds of the general formula (I):

in which R¹ represents hydrogen, halogen, (C₁-C₆)-alkyl, (C₁-C₆)-alkoxy,amino-(C₁-C₆)-alkyl or halogeno-(C₁-C₆)alkyl, R² and R³ are identical ordifferent and represent hydrogen, (C₁-C₆)alkoxy, (C₃-C₈)cycloalkyl orbiphenylaminocarbonyl, or represent (C₁-C₆)-alkyl which is optionallysubstituted by 1 to 3 substituents selected from the group consisting of(C₃-C₆)-cycloalkyl, (C₁-C₆)-alkoxy, halogen, hydroxyl, amino,tri-(C₁-C₆)-alkylsilyloxy, radicals of the formula

 in which R^(2′) represents hydrogen or (C₁-C₄)-alkyl,  a 5- or6-membered aromatic heterocycle having up to 3 heteroatoms from thegroup consisting of S, N and O, where a nitrogen-containing heterocyclemay also be attached via the nitrogen atom,  a 3- to 8-memberedsaturated or unsaturated nonaromatic heterocycle having up to 3heteroatoms from the group consisting of S, N and O, which mayoptionally be attached via a nitrogen atom, and  (C₆-C₁₀)-aryl which forits part may be substituted by hydroxyl or (C₁-C₆)-alkoxy, or  representa group of the formula

 in which R⁸ and R⁹ are identical to or different from one another andrepresent hydrogen and (C₁-C₄)-alkyl, or  represent a group of theformula

 in which R¹⁰ is the side-group of a naturally occurring α-amino acid,or  represent a group of the formula

 in which R¹¹ represents (C₁-C₄)-alkyl and R¹² represents hydrogen,(C₁-C₄)-alkyl or represents a group of the formula

 in which R^(10′) is the side-group of a naturally occurring α-aminoacid, or R² and R³ together with the nitrogen atom form a 5- or6-membered saturated heterocycle which may optionally contain an oxygenatom, R⁴ represents hydrogen, (C₁-C₆)-acyl, (C₂-C₆)-alkenyl,(C₃-C₈)-cycloalkyl, or R⁴ represents (C₁-C₆)-alkyl which may optionallybe substituted by 1 to 3 substituents selected from the group consistingof halogen, hydroxyl, (C₃-C₈)-cycloalkyl, (C₁-C₆)-acyl, (C₁-C₆)-alkoxy,carboxyl,

 in which R⁴ represents hydrogen, —(OCH₂CH₂),OCH₂CH₃, in which n is 0 or1, phenoxy, (C₆-C₁₀)-aryl and —NR³R¹⁴,  in which R¹³ and R¹⁴ areidentical or different and represent hydrogen, (C₁-C₆)-acyl,(C₁-C₆)-alkyl, carbamoyl, mono- or di-(C₁-C₆)-alkylamino-(C₁-C₆)-alkyl,mono- or di-(C₁-C₆)-alkylaminocarbonyl, (C₆-C₁₀)-aryl or(C₁-C₆)-alkoxycarbonyl, or  R¹³ and R¹⁴ together with the nitrogen atomform a 5- or 6-membered saturated heterocycle which may optionallycontain a further heteroatom from the group consisting of S and O or aradical of the formula —NR¹⁵, and which may be substituted by oxo,  inwhich R¹⁵ represents hydrogen or (C₁-C₄)-alkyl, or R⁴ represents(C₁-C₆)-alkyl which is substituted by a 5- or 6-membered aromatic,optionally benzo-fused heterocycle having up to 3 heteroatoms from thegroup consisting of S, N and O, where a nitrogen-containing heterocyclemay also be attached via the nitrogen atom, or which is substituted by radicals of the formulae

 in which R¹⁶ represents hydrogen or (C₁-C₆)-alkyl, R¹⁷ and R¹⁸ areidentical or different and represent hydrogen, (C₁-C₆)alkyl or(C₆-C₁₀)-aryl, where abovementioned (C₁-C₆)-alkyl and (C₆-C₁₀)-aryl mayoptionally be substituted by 1 to 3 substituents selected from the groupconsisting of hydroxyl, (C₁-C₆)-alkoxy and halogen, R⁵ representshydrogen, (C₁-C₆)-alkyl, halogen, amino, mono- or di-(C₁-C₆)-alkylaminoor represents (C₁-C₆)-alkanoylamino, R⁶ represents phenyl which mayoptionally be substituted by one to three substituents selected from thegroup consisting of halogen, (C₆-C₁₀)-aryl which may optionally besubstituted by 1 to 3 substituents selected from the group consisting of(C₁-C₆)-alkanoyl, (C₁-C₆)-alkoxy, (C₁-C₆)-alkyl, halogen,(C₁-C₆)-alkoxycarbonyl, nitro, halogeno-(C₁-C₆)-alkyl,halogeno-(C₁-C₆)-alkoxy, amino, (C₁-C₆)-alkylthio, hydroxyl, carboxyl,carbamoyl, mono- or di-(C₁-C₆)-alkylaminocarbonyl, mono- ordi-(C₁-C₆)-alkanoylamino, (C₁-C₆)-alkoxycarbonylamino,(C₁-C₆)-alkylsulphoxy, (C₁-C₆)-alkylsulphonyl,tri-(C₁-C₆)-alkylsilyloxy, a 3- to 8-membered saturated or unsaturatednonaromatic mono- or bicyclic heterocycle having up to 3 heteroatomsfrom the group consisting of S, N and O, which may optionally beattached via a nitrogen atom, and/or cyano, (C₁-C₆)-alkoxy,(C₁-C₆)-alkoxycarbonyl, (C₁-C₆)-alkylthio, hydroxyl, carboxyl, partiallyfluorinated (C₁-C₆)-alkoxy having up to 6 fluorine atoms, (C₁-C₆)-alkylwhich is optionally substituted by a radical of the formula

a 5- or 6-membered aromatic heterocycle having up to 3 heteroatoms fromthe group consisting of S, N and O which may optionally be attached viaa nitrogen atom and which may optionally be substituted by 1 to 3substituents selected from the group consisting of (C₁-C₆)-alkanoyl,(C₁-C₆)-alkoxy, (C₁-C₆)-alkyl, halogen, (C₁-C₆)-alkoxycarbonyl, nitro,halogeno-(C₁-C₆)-alkyl, halogeno-(C₁-C₆)-alkoxy, amino,(C₁-C₆)-alkylthio, hydroxyl, carboxyl, carbamoyl, aminocarbonyl, mono-or di-(C₁-C₆)-alkylaminocarbonyl, mono- or di-(C₁-C₆)-alkanoylamino,(C₁-C₆)-alkoxycarbonylamino, (C₁-C₆)-alkylsulphoxy,(C₁-C₆)-alkylsuphonyl, a 3- to 8-membered saturated or unsaturatednonaromatic mono- or bicyclic heterocycle having up to 3 heteroatomsfrom the group consisting of S, N and O which may optionally be attachedvia a nitrogen atom, and/or cyano, a 3- to 8-membered saturated orunsaturated nonaromatic mono- or bicyclic heterocycle having up to 3heteroatoms from the group consisting of S, N and O, which mayoptionally be attached via a nitrogen atom and which may optionally besubstituted by 1 to 3 substituents selected from the group consisting ofoxo, halogen, hydroxyl, (C₁-C₆)-alkoxycarbonyl,(C₁-C₆)-alkoxycarbonylamino, (C₁-C₆)-alkyl, halogeno-(C₁-C₆)-alkyl andhydroxy-(C₁-C₆)-alkyl, (C₂-C₆)-alkenyl  and groups of the formulae—OR¹⁹, —NR²⁰R²¹ or —CO—NR²²R²³, carbazole, dibenzofuran ordibenzothiophene, xanthene or 9,10-dihydroacridine,  in which R¹⁹ isphenyl which for its part is optionally substituted by a group of theformula —NR²⁴R²⁵  in which R²⁴ and R²⁵ are identical or different andrepresent hydrogen, (C₁-C₆)-alkyl or (C₁-C₆)-acyl, or R¹⁹ represents(C₁-C₆)-alkyl which is optionally mono- to trisubstituted by hydroxyland/or halogen, R²⁰ and R²¹ are identical or different and representhydrogen, carbamoyl, mono- or di-(C₁-C₆)-alkylaminocarbonyl, phenyl,(C₁-C₆)-acyl or (C₁-C₆)-alkyl, where abovementioned (C₁-C₆)-alkyl isoptionally substituted by (C₁-C₆)-alkoxy, (C₁-C₆)-acyl, by phenyl or bya 5- or 6-membered aromatic heterocycle having up to 3 heteroatoms fromthe group consisting of S, N and O, where abovementioned phenyl andabovementioned aromatic heterocycle are optionally mono- totrisubstituted by identical or different substituents from the groupconsisting of halogen and hydroxyl, and R²² and R²³ are identical ordifferent and represent hydrogen or (C₁-C₆)-alkyl, and R⁷ may have themeaning of R⁵ and may be identical to or different from R⁵,  and theirsalts.
 2. Compounds of the general formula (I) according to claim 1:

in which R¹ represents hydrogen, halogen, (C₁-C₆)-alkyl, (C₁-C₆)-alkoxy,amino-(C₁-C₆)-alkyl or halogeno-(C₁-C₆)-alkyl, R² and R³ are identicalor different and represent hydrogen, (C₁-C₆)-alkoxy, (C₃-C₈)-cycloalkylor biphenylaminocarbonyl, or  represent (C₁-C₆)-alkyl which isoptionally substituted by 1 to 3 substituents selected from the groupconsisting of (C₃-C₆)-cycloalkyl, (C₁-C₆)-alkoxy, halogen, hydroxyl,amino, radicals of the formula

 a 5- or 6-membered aromatic heterocycle having up to 3 heteroatoms fromthe group consisting of S, N and O, where a nitrogen-containingheterocycle may also be attached via the nitrogen atom,  a 3- to8-membered saturated or unsaturated nonaromatic heterocycle having up to3 heteroatoms from the group consisting of S, N and O, which mayoptionally be attached via a nitrogen atom, and  (C₆-C₁₀)-aryl, whichfor its part may be substituted by hydroxyl or (C₁-C₆)-alkoxy, or represent a group of the formula

 in which R⁸ and R⁹ are identical to or different from one another andrepresent hydrogen and (C₁-C₄)-alkyl, or  represent a group of theformula

 in which R¹⁰ is the side-group of a naturally occurring α-amino acid,or  represent a group of the formula

 in which R¹¹ represents (C₁-C₄)-alkyl and R¹² represents hydrogen,(C₁-C₄)-alkyl or represents a group of the formula

 in which R^(10′) is the side-group of a naturally occurring α-aminoacid, or R² and R³ together with the nitrogen atom form a 5- or6-membered saturated heterocycle which may optionally contain an oxygenatom, R⁴ represents hydrogen, (C₁-C₆)-acyl, (C₂-C₆)-alkenyl,(C₃-C₈)-cycloalkyl, or R⁴ represents (C₁-C₆)-alkyl which may optionallybe substituted by 1 to 3 substituents selected from the group consistingof halogen, hydroxyl, (C₁-C₆)-acyl, (C₁-C₆)alkoxy, —(OCH₂CH₂)_(n)OCH₂CH₃, in which n is 0 or 1, phenoxy, (C₆-C₁₀)-aryl and—NR³R¹⁴, in which R¹³ and R¹⁴ are identical or different and representhydrogen, (C₁-C₆)-acyl, (C₁-C₆)-alkyl, carbamoyl, mono- ordi-(C₁-C₆)-alkylamino-(C₁-C₆)-alkyl, mono- ordi-(C₁-C₆)-alkylaminocarbonyl, (C₆-C₁₀)-aryl or (C₁-C₆)-alkoxycarbonyl,or R¹³ and R¹⁴ together with the nitrogen atom form a 5- or 6-memberedsaturated heterocycle which may optionally contain a further heteroatomfrom the group consisting of S and O or a radical of the formula —NR¹⁵and which may be substituted by oxo, in which R¹⁵ represents hydrogen or(C₁-C₄)-alkyl, or R⁴ represents (C₁-C₆)-alkyl which is substituted by a5- or 6-membered aromatic, optionally benzo-fused heterocycle having upto 3 heteroatoms from the group consisting of S, N and O, where anitrogen-containing heterocycle may also be attached via the nitrogenatom, or which is substituted by radicals of the formulae

 in which R¹⁶ represents hydrogen or (C₁-C₆)-alkyl, R¹⁷ and R¹⁸ areidentical or different and represent hydrogen, (C₁-C₆)-alkyl or(C₆-C₁₀)-aryl, where abovementioned (C₁-C₆)-alkyl and (C₆-C₁₀)-aryl mayoptionally be substituted by 1 to 3 substituents selected from the groupconsisting of hydroxyl, (C₁-C₆)-alkoxy and halogen, R⁵ representshydrogen, (C₁-C₆)-alkyl, halogen, amino, mono- or di-(C₁-C₆)-alkylaminoor represents (C₁-C₆)-alkanoylamino, R⁶ represents phenyl which mayoptionally be substituted by one to three substituents selected from thegroup consisting of halogen, (C₆-C₁₀)-aryl which may optionally besubstituted by 1 to 3 substituents selected from the group consisting of(C₁-C₆)-alkanoyl, (C₁-C₆)-alkoxy, (C₁-C₆)-alkyl, halogen,(C₁-C₆)-alkoxycarbonyl, nitro, halogeno-(C₁-C₆)-alkyl,halogeno-(C₁-C₆)-alkoxy, amino, (C₁-C6)-alkylthio, hydroxyl, carboxyl,carbamoyl, mono- or di-(C₁-C₆)-alkylaminocarbonyl, mono- ordi-(C₁-C₆)-alkanoylamino, (C₁-C₆)-alkoxycarbonylamino,(C₁-C₆)-alkylsulphoxy, (C₁-C₆)-alkylsulphonyl,tri-(C₁-C₆)-alkylsilyloxy, a 3- to 8-membered saturated or unsaturatednonaromatic mono- or bicyclic heterocycle having up to 3 heteroatomsfrom the group consisting of S, N and O, which may optionally beattached via a nitrogen atom, and/or cyano, (C₁-C₆)-alkoxy,(C₁-C₆)-alkoxycarbonyl, (C₁-C₆)-alkylthio, hydroxyl, carboxyl, partiallyfluorinated (C₁-C₆)-alkoxy having up to 6 fluorine atoms, (C₁-C₆)-alkylwhich is optionally substituted by a radical of the formula

a 5- or 6-membered aromatic heterocycle having up to 3 heteroatoms fromthe group consisting of S, N and O which may optionally be attached viaa nitrogen atom and which may optionally be substituted by 1 to 3substituents selected from the group consisting of (C₁-C₆)-alkanoyl,(C₁-C₆)-alkoxy, (C₁-C₆)-alkyl, halogen, (C₁-C₆)-alkoxycarbonyl, nitro,halogeno-(C₁-C₆)-alkyl, halogeno-(C₁-C₆)-alkoxy, amino,(C₁-C₆)-alkylthio, hydroxyl, carboxyl, carbamoyl, mono- ordi-(C₁-C₆)-alkylaminocarbonyl, mono- or di-(C₁-C₆)alkanoylamino,(C₁-C₆)-alkoxycarbonylamino, (C₁-C₆)-alkylsulphoxy,(C₁-C₆)-alkylsuphonyl, a 3- to 8-membered saturated or unsaturatednonaromatic mono- or bicyclic heterocycle having up to 3 heteroatomsfrom the group consisting of S, N and O which may optionally be attachedvia a nitrogen atom, and/or cyano, a 3- to 8-membered saturated- orunsaturated nonaromatic mono- or bicyclic heterocycle having up to 3heteroatoms from the group consisting of S, N and O, which mayoptionally be attached via a nitrogen atom and which may optionally besubstituted by 1 to 3 substituents selected from the group consisting ofoxo, halogen, hydroxyl, (C₁-C₆)-alkoxycarbonyl,(C₁-C₆)-alkoxycarbonylamino, (C₁-C₆)-alkyl, halogeno-(C₁-C₆)-alkyl andhydroxy-(C₁-C₆)-alkyl, (C₂-C₆)-alkenyl  and groups of the formulae—OR¹⁹, —NR²⁰R²¹ or —CO—NR²²R²³,  in which R¹⁹ is phenyl which for itspart is optionally substituted by a group of the formula —NR²⁴R²⁵,  inwhich R²⁴ and R²⁵ are identical or different and represent hydrogen,(C₁-C₆)-alkyl or (C₁-C₆)-acyl, or R¹⁹ represents (C₁-C₆)-alkyl which isoptionally mono- to trisubstituted by hydroxyl and/or halogen, R²⁰ andR²¹ are identical or different and represent hydrogen, carbamoyl, mono-or di-(C₁-C₆)-alkylaminocarbonyl, phenyl, (C₁-C₆)-acyl or (C₁-C₆)-alkyl, where abovementioned (C₁-C₆)-alkyl is optionally substituted by(C₁-C₆)-alkoxy, (C₁-C₆)-acyl, by phenyl or by a 5- or 6-memberedaromatic heterocycle having up to 3 heteroatoms from the groupconsisting of S, N and O, where abovementioned phenyl and abovementionedaromatic heterocycle are optionally mono- to trisubstituted by identicalor different substituents from the group consisting of halogen andhydroxyl, and R²² and R²³ are identical or different and representhydrogen or (C₁-C₆)-alkyl, and R⁷ may have the meaning of R⁵ and may beidentical to or different from R⁵, and their salts.
 3. Compounds of thegeneral formula (I) according to claim 1 or 2, in which R¹ representshydrogen or (C₁-C₆)-alkyl.
 4. Compounds of the general formula (I)according to any of claims 1, 2 and 3, in which R² and R³ eachindependently represent hydrogen or (C₁-C₆)-alkyl.
 5. Compounds of thegeneral formula (I) according to any of claims 1, 2, 3 and 4, in, whichR⁴ represents hydrogen or (C₁-C₆)-alkyl.
 6. Compounds of the generalformula (I) according to any of claims 1, 2, 3, 4 and 5, in which R⁵represents hydrogen.
 7. Compounds of the general formula (I) accordingto any of claims 1, 2, 3, 4, 5 and 6, in which R⁶ represents phenylwhich may optionally be substituted by one to three substituentsselected from the group consisting of halogen, (C₆-C₁₀)-aryl which mayoptionally be substituted by 1 to 3 substituents selected from the groupconsisting of (C₁-C₆)-alkanoyl, (C₁-C₆)-alkoxy, (C₁-C₆)-alkyl, halogen,(C₁-C₆)-alkoxycarbonyl, nitro, halogeno-(C₁-C₆)-alkyl,halogeno-(C₁-C₆)-alkoxy, amino, hydroxyl, mono- ordi-(C₁-C₆)-alkylamino, mono- or di-(C₁-C₆)-alkanoylamino,(C₁-C₆)-alkoxycarbonylamino, and/or cyano, a 5- or 6-membered aromaticheterocycle having up to 3 heteroatoms from the group consisting of S, Nand O, which may optionally be attached via a nitrogen atom. 8.Compounds according to claim 1 having the following formula:

in which R¹, R², R³, R⁴, R⁵ and R⁷ are each as defined in claim 1, R²⁶and R²⁷ are identical or different and represent hydrogen, halogen,(C₁-C₆, alkoxy, (C₁-C₆)-alkoxycarbonyl, (C₁-C₆)-alkylthio, hydroxyl,carboxyl, partially fluorinated (C₁-C₆)-alkoxy having up to 6 fluorineatoms, (C₁-C₆)-alkyl, a group of the formulae —OR¹⁹, —NR²⁰R²¹ or—CO—NR²²R²³, in which R¹⁹ represents phenyl which for its part isoptionally substituted by a group of the formula —NR²⁴R²⁵,  in which R²⁴and R²⁵ are identical or different and represent hydrogen, (C₁-C₆)-alkylor (C₁-C₆)-acyl, or R¹⁹ represents (C₁-C₆)-alkyl which is optionallymono- to trisubstituted by hydroxyl and/or halogen, R²⁰ and R²¹ areidentical or different and represent hydrogen, carbamoyl, mono- ordi-(C₁-C₆)-alkylaminocarbonyl, phenyl, (C₁-C₆)-acyl or (C₁-C₆)-alkyl, where abovementioned (C₁-C₆)-alkyl is optionally substituted by(C₁-C₆)-alkoxy, (C₁-C₆)-acyl, phenyl or by a 5- or 6-membered aromaticheterocycle having up to 3 heteroatoms from the group consisting of S, Nand O, where abovementioned phenyl and abovementioned aromaticheterocycle are optionally mono- to trisubstituted by identical ordifferent substituents from the group consisting of halogen andhydroxyl, and R²² and R²³ are identical or different and representhydrogen or (C₁-C₆)-alkyl, R²⁸ represents (C₆-C₁₀)-aryl, which mayoptionally be substituted by 1 to 3 substituents selected from the groupconsisting of (C₁-C₆)-alkanoyl, (C₁-C₆)-alkoxy, (C₁-C₆)alkyl, halogen,(C₁-C₆)-alkoxycarbonyl, nitro, halogen-(C₁-C₆)-alkyl,halogen-(C₁-C₆)-alkoxy, amino, (C₁-C₆)-alkylthio, hydroxyl, carboxyl,carbamoyl, mono- or di-(C₁-C₆)-alkylaminocarbonyl, mono- ordi-(C₁-C₆)-alkanoylamino, (C₁-C₆)-alkoxycarbonylamino,(C₁-C₆)-alkylsulphoxy, (C₁-C₆)-alkylsulphonyl,tri-(C₁-C₆)-alkylsilyloxy, a 3- to 8-membered saturated or unsaturatednonaromatic mono- or bicyclic heterocycle having up to 3 heteroatomsfrom the group consisting of S, N and O, which may optionally beattached via a nitrogen atom, and/or cyano, or R²⁸ represents a 5- or6-membered aromatic heterocycle having up to 3 heteroatoms from thegroup consisting of S, N and O, which may optionally be attached via anitrogen atom and which may optionally be substituted by 1 to 3substituents selected from the group consisting of (C₁-C₆)-alkanoyl,(C₁-C₆)-alkoxy, (C₁-C₆)-alkyl, halogen, (C₁-C₆)-alkoxycarbonyl, nitro,halogeno-(C₁-C₆)-alkyl, halogeno-(C₁-C₆)-alkoxy, amino,(C₁-C₆)-alkylthio, hydroxyl, carboxyl, carbamoyl, mono- ordi-(C₁-C₆)-alkylaminocarbonyl, mono- or di-(C₁-C₆)-alkanoylamino,(C₁-C₆)-alkoxycarbonylamino, (C₁-C₆)-alkylsulphoxy,(C₁-C₆)-alkylsulphonyl, a 3- to 8-membered saturated or unsaturatednonaromatic mono- or bicyclic heterocycle having up to 3 heteroatomsfrom the group consisting of S, N and O, which may optionally beattached via a nitrogen atom, and/or cyano, and their salts.
 9. Compoundaccording to claim 1 of the formula:

and pharmaceutically acceptable salts thereof.
 10. Compound according toclaim 1 of the formula:

and pharmaceutically acceptable salts thereof.
 11. Compound according toclaim 1 of the formula:

and pharmaceutically acceptable salts thereof.
 12. Compound according toclaim 1 of the formula:


13. Compound according to claim 1 of the formula:


14. Compounds of the general formula (IV)

in which R¹, R⁴, R⁵, R⁶ and R⁷ are each as defined in claim 1 and D is ahalogen atom.
 15. Process for preparing the compounds of the generalformula (I) according to claim 1, characterized in that [A] compounds ofthe general formula (II)

 in which R¹, R², R³ and R⁴ are each as defined in claim 1, are reactedwith compounds of the general formula (III)

 in which A represents a leaving group and R⁵, R⁶ and R⁷ are each asdefined in claim 1, in inert solvents, if appropriate in the presence ofa base and/or an auxiliary, or [B] compounds of the general formula (IV)

 in which R¹, R⁴, R⁵, R⁶ and R⁷ are each as defined in claim 1 and D isa halogen atom, preferably chlorine, are reacted with amines of thegeneral formula (V), HNR²R³ in which R² and R³ are each as defined inclaim 1, in inert solvents, [C] compounds of the general formula (X)

in which R¹, R², R³, R⁴, R⁵, R⁷, R²⁶ and R²⁷ are each as defined aboveand E is trifluoromethanesulphonate or halogen, are reacted with boronicacids or stannanes of the general formula (XI): R²⁸M  (XI), in which R²⁸is as defined above and M may be, for example, atri-(C₁-C₆)-alkylstannyl group or a boronic acid group, in inertsolvents in the presence of palladium catalysts, if appropriate in thepresence of base, at temperatures of 50-140° C., to give compounds ofthe formula (XIV)

and [D] compounds of the general formula (XII)

in which R¹, R², R³, R⁴, R⁵, R⁷, R²⁶ and R²⁷ are each as defined aboveand M is as defined above, are reacted with trifluoromethanesulphonatesor halides of the general formula (XIII): R²⁸E  (XIII), in which R²⁸ isas defined above and E is as defined above, in inert solvents in thepresence of palladium catalysts, if appropriate in the presence of abase, at temperatures of 50-140° C., to give compounds of the formula(XIV).
 16. Compounds according to claim 1 for use as medicaments. 17.Pharmaceutical composition, comprising a compound of the general formula(I) according to claim 1 in a mixture with a pharmaceutically acceptablecarrier or excipient.
 18. Use of a compound of the general formula (I)according to claim 1 for preparing a medicament.
 19. Use of a compoundof the general formula (I) according to claim 1 for preparing amedicament for treating viral infections.
 20. Use of a compound of thegeneral formula (I) according to claim 1 for preparing a medicament fortreating viral infections caused by herpes viruses.
 21. Use of acompound of the general formula (I) according to claim 1 for preparing amedicament for treating viral infections caused by Herpes simplexviruses.
 22. Use of N-[5-(aminosulphonyl)-1,3-thiazol-2-yl]acetamidederivatives for preparing medicaments.
 23. Use ofN-[5-(aminosulphonyl)-1,3-thiazol-2-yl]-2-phenylacetamide derivativesfor preparing medicaments.
 24. Use ofN-[5-(aminosulphonyl)-1,3-thiazol-2-yl]-2-[1,1′-biphenyl]-4-ylacetamidederivatives for preparing medicaments.
 25. Use according to any ofclaims 22, 23 and 24 for preparing compositions for the treatment and/orprevention of viral infections in humans or animals.
 26. Use accordingto any of claims 22, 23 and 24 for preparing compositions for thetreatment and/or prevention of viral infections caused by herpes virusesin humans or animals.
 27. Use according to any of claims 22, 23 and 24for preparing compositions for the treatment and/or prevention of viralinfections caused by Herpes simplex viruses in humans or animals.